Compositions, kits and methods for nutrition supplementation

ABSTRACT

A method for improving a nutritional status in a prenatal, pregnant or breastfeeding patient. The method includes providing a pharmaceutical composition in a single oral dosage form for administration to a prenatal, pregnant or breastfeeding patient. The pharmaceutical composition consists of vitamin D, iodine, vitamin B1, vitamin B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitamin E, vitamin A, vitamin C, iron, zinc, copper, magnesium, omega-3 fatty acids and one or more pharmaceutically acceptable carriers. The method further includes providing a daily dosage regimen for administering the single oral dosage form to the patient to improve a nutritional status in the patient.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a continuation of and claims the benefit,under 35 U.S.C. §120, of U.S. patent application Ser. No. 13/475,182,which is a continuation U.S. patent application Ser. No. 13/292,735,filed Nov. 9, 2011, issued as U.S. Pat. No. 8,183,227 on May 22, 2012,which claims the benefit under 35 U.S.C. §119 of U.S. Provisional PatentApplication Ser. No. 61/505,341, filed Jul. 7, 2011. The entire contentsof each of these applications are incorporated herein by reference as ifset forth herein.

FIELD OF THE INVENTION

The present invention relates to various vitamin, nutrient and mineralcompositions and kits for nutritional supplementation and methods ofadministration of compositions and kits for nutritional supplementationin, for example, subjects in physiologically stressful states, such asoccur during pregnancy, lactation, or in need thereof.

BACKGROUND OF THE INVENTION

Nutrition plays a critical role in maintaining good health. Propernutrition prevents dietary deficiencies, and also protects against thedevelopment of disease. When the body faces physiological stress, propernutrition plays an increasingly important role. For example, pregnancyand lactation are among the most nutritionally volatile andphysiologically stressful periods and processes in the lifetimes ofwomen. Vitamin and mineral needs are almost universally increased duringthese natural processes. Increased vitamin and mineral needs duringthese times are almost always due to elevated metabolic demand,increased plasma volume, increased levels of blood cells, decreasedconcentrations of nutrients, and decreased concentrations ofnutrient-binding proteins.

When increased nutrient needs occur during pregnancy, lactation, or anyother physiologically stressful state, nutritional supplementationserves a vital role in maintaining good health. Nutritionalsupplementation is especially pertinent to women contemplatingconceiving a child because optimizing specific nutrients before, during,and after the physiological processes of pregnancy or lactation can haveprofound, positive, and comprehensive impacts upon the overall wellnessof the developing and newborn child as well as on the safety and healthof the mother. The present invention provides compositions, kits andmethods designed to supplement the nutritional needs of individuals inphysiologically stressful states.

Supplementation with certain vitamins and minerals serves a role inprotecting against disease and contributes to the overall health of themother and developing child. Specifically, vitamins, nutrients andminerals such as vitamin D, iodine, vitamin B1, vitamin B6, vitamin B12,vitamin B2, vitamin B9, vitamin B3, vitamin E, vitamin A, vitamin C,iron, zinc, copper, magnesium, and omega 3 fatty acids such asdocosahexaenoic acid (DHA), play integral roles in physiologicalmechanisms that serve to prevent, treat and/or alleviate the occurrenceor negative effects of some diseases.

Iodine also provides nutritional benefits as it is an essentialcomponent of the thyroid hormones that are involved in the regulation ofvarious enzymes and metabolic processes, such as thyroxine andtriiodothyronine. Indeed, iodine deficiency disorders (IDD) includemental retardation, hypothyroidism, goiter, cretinism, and varyingdegrees of other growth and developmental abnormalities which can be aresult from inadequate thyroid hormone production from lack ofsufficient iodine. See, for example, Food and Nutrition Board andInstitute of Medicine, DIETARY REFERENCE INTAKES FOR VITAMIN A, VITAMINK, ARSENIC, BORON, CHROMIUM, COPPER, IODINE, IRON, MANGANESE,MOLYBDENUM, NICKEL, SILICON, VANADIUM, AND ZINC (2001), page 260.Further, iodine is an important element in breast milk for infantnutrition. An adequate concentration of iodine in breast milk isessential to provide for optimal neonatal thyroid hormone stores and toprevent impaired neurological development in breast-fed neonates. Inmany countries of the world, low iodine content of the breast milkindicates less than optimum maternal and infant iodine nutrition. F.Azizi et al., CLIN ENDOCRINOL, 70(5):803-9 (2009). Multivitamin andmulti nutritional supplements, for example for prenatal pregnant orbreast-feeding women, are also lacking or deficient in the dosage amountof this important mineral.

In another example, there is a need for a nutritional supplement withincreased vitamin D, in for example, a prenatal or dietary supplement,as recent research suggests that vitamin D has more positivephysiological effects than previous thought, in for example prenatal andpregnant women. It has recently been determined that vitamin D haspreviously unknown roles in the enhancement of vascular function,defense against cancer, immuno-competence, blood pressure regulation andpossessing the ability to enhance cellular insulin sensitivity in thehuman body. Due to the additional roles that vitamin D plays in thehuman body, it has recently been determined that higher daily vitamin Dintake beyond current recommendations may be associated with betterhealth outcomes. Indeed, studies suggest increasing the serum level of25-hydroxyvitamin D, a beneficial derivative of vitamin D, to a 30 ng/mlserum range. A 30 ng/ml appears to be the most advantageous serum levelin recent studies reviewing patient bone mineral density (BMD), lowerextremity function, dental health, risk of falls, admission to nursinghome, fractures, cancer prevention and incident hypertension.Bischoff-Ferrari H A, ADV EXP MED BIOL. 624:55-71 (2008). Effective andsafe doses of vitamin D to bring serum levels of 25-hydroxyvitamin D upto a desirable level of 30 ng/ml is currently needed.

Lastly, a present problem with nutritional supplements that includemultiple vitamins, nutrients and minerals is the ability to include allthe components in one composition. Providing a single compositionmultivitamin and multinutrient supplement is an appealing featurebecause it improves patient compliance. Patients, and specifically forexample, pregnant patients, often have nausea, and may have difficultyswallowing nutritional supplements. Compliance issues regarding takingmultiple pills may therefore result. A one pill or one compositionnutritional supplement that includes the beneficial vitamins, nutrientsand minerals in appropriate dosage amounts would thus be beneficial forimproving patient compliance in for example, pregnant women. Adifficulty in the nutrition supplement market, however, is the abilityto include multiple vitamins, minerals and nutrients of various water orfat solubilities in the needed dosage amounts all in one composition.For example, nutritional supplements that include fat soluble compoundssuch as DHA and water soluble vitamins such as B-complex vitamins andvitamin C, are often separated into multiple compositions. A supplementcomprising multiple vitamins, nutrients and minerals blended to form asingle composition, is thus currently needed. In a specific example, thesingle composition may be in the form of a gelcap. Patient compliance isalso improved if a gelcap is used to administer the drug because of itssoft and elastic nature, which makes it easier to swallow compared to ahard tablet or caplet.

A liquid gelcap also has numerous advantages. First, it retains many ofthe advantages of consumer acceptance and is easier to swallow due tothe outer coating being a soft and elastic gelatin shell. Also,concentrated liquid compositions are well suited for encapsulationwithin a soft gelatin shell, creating flexibility that further assistsin the capsule being easier to swallow. The active drug contained in theliquid form also provides advantages by dispersing the drug to theactive site. For example, the active drug does not first have todissolve in the gastrointestinal tract, thereby facilitating absorptionof the pharmacologically active substance. See, for example, U.S. Pat.No. 6,689,382, which is expressly incorporated by reference herein.Other formulations take advantage of the liquid form by creating asustained release gelatin capsule, thereby permitting the delivery ofthe drug in a controlled fashion. See, for example, U.S. Pat. Nos.5,324,280 and 6,929,803, which are expressly incorporated by referenceherein.

SUMMARY OF THE INVENTION

The present invention provides compositions and methods of administeringcompositions for both prophylactic and therapeutic nutritionalsupplementation. Specifically, for example, the present inventionrelates to novel compositions of vitamins, minerals, and omega-3 fattyacids that can be used to supplement the nutritional deficienciesobserved in patients throughout physiologically stressful states, which,in certain embodiments of the present invention, include prenatal,pregnant and breast-feeding women.

One embodiment of the present invention may include a nutritionalsupplement wherein multiple vitamins, minerals and nutrients areprovided in one composition. In one embodiment of the present invention,the composition may comprise vitamin D, iodine, vitamin B1, vitamin B6,vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitamin E, vitamin A,vitamin C, iron, zinc, copper, magnesium, omega 3 fatty acids and one ormore pharmaceutically acceptable carriers.

In one embodiment of the present invention, vitamin D may be included inthe form selected from one or more of the group consisting of vitamin D3(calciol or cholecalciferol or colecalciferol), vitamin D2 (calciferol,ergocalciol, ergocalciferol, ercalciol, Deltalin or Viosterol),previtamin D2, ergosterol, calcitriol (1,25-dihydroxycholecalciferol),7-dehydrocholesterol, vitamin D1, vitamin D4 (also known as22-dihydroergocalciferol, 22,23-dihydroercalciol or(24S)-methylcalciol), vitamin D5 (also known as (24S)-Ethylcalciol orsitocalciferol), 7-dehydrositosterol, Lumisterol, 25-hydroxyvitamin D,all steroids that exhibit the biological activity of calciol,25-fluorocalciol, (3S)-3-amino-3-deoxycalciol, 11α-acetoxycalciol,calcidiol (25-hydroxycholecalciferol or calcifediol), ercalcitriol,calcitetrol, tacalciol (tachysterol3), (5E)-isocalciol (isovitamin D3),Dihydroercalciol (dihydrotachysterol3), (1S)-Hydroxycalciol (also knownas 1α-hydroxycholecalciferol or alfacaleidol), (24R)-Hydroxycalcidiol(also known as 24(R),25-dihydroxycholecalciferol), Ercalcidiol,Ercalcitriol, Ertacalciol, (5E)-(10S)-10,19-Dihydroercalciol(dihydrotachysterol2), (6Z)-Tacalciol (precalciferol or pre-vitamin D),and (22E)-(24R)-Ethyl-22,23-didehydrocalciol (vitamin D6).

In another embodiment, the compositions may include vitamin B1 in theform selected from one or more of the group consisting of thiamine,thiamine monophosphate, thiamine diphosphate, thiamine triphosphate,acetiamine, allithiamine, prosultiamine and S-acyl derivatives ofthiamine such as benfotiamine, fursultiamine and salts and estersthereof. In another embodiment, the compositions may include vitamin B1in the form selected from one or more of the group consisting ofthiamine, thiamine monophosphate, thiamine diphosphate, thiaminetriphosphate, acetiamine, allithiamine, prosultiamine and S-acylderivatives of thiamine such as benfotiamine, fursultiamine and saltsand esters thereof.

In another embodiment, the compositions may include vitamin A in theform selected from one or more of the group consisting of retinolacetate (retinyl acetate or vitamin A acetate), retinol (vitamin Aalcohol), retinol palmitate (retinyl palmitate or vitamin A palmitate),retinoic acid (tretinoin), retinal, beta-cryptoxanthin, alpha-carotene,beta-carotene, gamma-carotene, and provitamin A carotenoids. In aspecific embodiment, vitamin A may be included in the form of betacarotene.

In another embodiment, the compositions may include vitamin B9 in theform selected from one or more of the group consisting of folic acid,folinic acid, folacin, metafolin, and/or one or more natural isomers offolate including (6S)-tetrahydrofolic acid or a polyglutamyl derivativethereof, (6S,R)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5-methyl-(6S,R)-tetrahydrofolic acid or a polyglutamylderivative thereof, 5-formyl-(6S)-tetrahydrofolic acid or a polyglutamylderivative thereof, 10-formyl-(6R)-tetrahydrofolic acid or apolyglutamyl derivative thereof, 5,10-methylene-(6R)-tetrahydrofolicacid or a polyglutamyl derivative thereof,5,10-methenyl-(6R)-tetrahydrofolic acid or a polyglutamyl derivativethereof and 5-formimino-(6S)-tetrahydrofolic acid or a polyglutamylderivative thereof and their salts and esters thereof. In anotherembodiment, the compositions may include vitamin B2 in the form selectedfrom one or more of the group consisting of flavin mononucleotide (FMN),flavin adenine dinucleotide (FAD), riboflavin (also known as7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavinderivatives such as riboflavin-5′-monophosphate,riboflavin-5′-monobutyrate and riboflavin-5′-monopalmitate.

In another embodiment, the compositions may include vitamin B3 in theform selected from one or more of the group consisting of niacin(nicotinic acid or pyridine-3-carboxylic acid), and nicotinamide(niacinamide) and salts and esters thereof. In another embodiment, thecompositions may include vitamin B6 in the form selected from one ormore of the group consisting of pyridoxine,3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine, 5′-deoxypyridoxal,2-demethylpyridoxal(2-norpyridoxal), 2-propyl-2-norpyridoxal(2′-ethylpyridoxal), 6-methylpyridoxal, 2′-hydroxypyridoxal(2-hydroxymethyl-2-demethylpyridoxal or 2-hydroxymethyl-2-norpyridoxal),4′-deoxypyridoxine 5′-phosphate, 5′-methylpyridoxal-5′-phosphate,pyridoxal N-oxide 5′-phosphate, Pyridoxal, Pyridoxamine,Pyridoxine-5′-phosphate (PNP), pyridoxal-5′-phosphate (PLP) andpyridoxamine-5′-phosphate (PMP), and their salts and chelates thereof.In another embodiment, the compositions may include vitamin B12 in theform selected from one or more of the group consisting of cobalamin,methylcobalamin, 5′-deoxyadenosylcobalamin (adenosylcobalamin orcobamamide), cyanocobalamin, hydroxycobalamin and mecobalamin.

In another embodiment, the compositions may include vitamin E in theform selected from one or more of the group consisting of alpha, beta,gamma, and delta tocopherols in its natural or synthetic (dl) forms;alpha, beta, gamma, and delta tocotrienols in its natural or synthetic(dl) forms, dl-alpha tocopheryl derivatives such as dl-alpha tocopherylesters, dl-alpha-tocopheryl acetate or succinate and d-alpha-tocopherylacetate or dl-alpha tocopheryl phosphates (such as Ester-E®). In anotherembodiment, the compositions may include vitamin C in the form selectedfrom one or more of the group consisting of ascorbic acid, ascorbates(calcium or sodium ascorbate), dehydroascorbic acid and salts, ascorbylpalmitate, ascorbyl phosphates and salts (such as sodium or magnesiumascorbyl phosphate), ascorbyl tetraisopalmitate, tetrahexyldecylascorbate, ascorbyl sulfates and salts, acylated ascorbic acidderivatives (such as 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbicacids), 6-bromo-6-deoxy-L-ascorbic acid, and ascorbate salts. In anotherembodiment, the compositions may include iron in the form selected fromone or more of the group consisting of elemental iron, in the form of asalt, chelated form, non-chelated form, chelated to an amino acid,carbonyl iron, ferrous gluconate, ferrous fumarate, polysaccharide ironcomplex, elemental polysaccharide iron, polysaccharide iron, ferrous(II)-bis-glycinate chelate, ferrous asparto glycinate, ferrousbisglycinate, ferrous bisglycinate hydrochloride, ferrous bisglycinate,elemental ferrous bisglycinate, ferrous sulfate, ferronyl (micronized),as Iron Aid, iron protein succinylate, carbonyl iron, Sumalate iron,Heme iron complex, as Ferrochel amino acid chelate, Heme ironpolypeptide as Proferrin-bovine source, as Heme iron polypeptide (bovinesource) as sodium iron EDTA (Ferrazone), ferric ammonium citrate,elemental iron, and ferric pyrophosphate.

In another embodiment, the compositions may include zinc in the formselected from one or more of the group consisting of elemental zinc, inthe form of a salt, in a chelated form, in a non-chelated form, zincacetate, zinc gluconate, zinc picolinate, zinc sulfate and zinc oxide.In another embodiment, the compositions may include copper in the formselected from one or more of the group consisting of elemental copper,in the form of a salt, in a chelated form, in a non-chelated form,cupric oxide, copper sulfate, copper gluconate, copper citrate, cupricacetate, alkaline copper carbonate, and copper salicylate. In anotherembodiment, the compositions may include magnesium in the form selectedfrom one or more of the group consisting of elemental magnesium, in theform of a salt, in a chelated form, in a non-chelated form, magnesiumacetate, magnesium carbonate, magnesium gluconate, magnesium chloride,magnesium citrate, magnesium silicate, magnesium stearate, magnesiumsulfate, magnesium oxide, and magnesium chelated to an amino acid(magnesium glycinate, magnesium aspartate).

In another embodiment, the compositions may include omega 3 fatty acidsin the form selected from one or more of the group consistingdocosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and α-linolenicacid (ALA). In a specific embodiment of the present invention, omega-3fatty acids may comprise DHA. In a specific embodiment, the source ofDHA is algae oil. In one specific embodiment, the source of the algaeoil is microalgae Crypthecodinium cohnii.

In another embodiment, the compositions may include iodine in the formselected from one or more of the group consisting of iodide, elementaliodine, iodized salt, Lugol's iodine, sodium iodide, potassium iodide,potassium iodate, nascent iodine, and Nano-Colloidal Detoxified Iodine.

In an embodiment, the compositions may include vitamin D in an amount ofabout 500 I.U. to about 1500 I.U., iodine in an amount of about 75 μg toabout 225 μg, vitamin B1 in an amount of about 0.8 mg to about 2.4 mg,vitamin B6 in an amount of about 1.2 mg to about 3.8 mg, vitamin B12 inan amount of about 6 μg to about 18 μg, vitamin B2 in an amount of about0.9 mg to about 2.7 mg, vitamin B9 in an amount of about 0.5 mg to about1.5 mg, vitamin E in an amount of about 10 I.U. to about 30 I.U.,vitamin A in an amount of about 550 I.U. to about 1650 I.U., vitamin Cin an amount of about 15 mg to about 45 mg, vitamin B3 in an amount ofabout 7.5 mg to about 22.5 mg, iron in an amount of about 14.5 mg toabout 43.5 mg, zinc in an amount of about 12.5 mg to about 37.5 mg,copper in an amount of about 1.0 mg to about 3.0 mg, magnesium in anamount of about 10 mg to about 30 mg, and omega 3 fatty acids in anamount of about 100 mg to about 300 mg.

In a specific embodiment, vitamin D may be in the form of vitamin D3 andmay be present in an amount of about 1000 I.U. or 25 μg. In a specificembodiment, iodine may be present in an amount of about 150 μg. In aspecific embodiment, vitamin B1 may be present in an amount of about 1.6mg. In a specific embodiment, vitamin B6 may be present in an amount ofabout 2.5 mg. In a specific embodiment, vitamin B12 may be present in anamount of about 12 μg. In a specific embodiment, vitamin B2 may bepresent in an amount of about 1.8 mg. In a specific embodiment, vitaminB9 may be present in an amount of about 1.0 mg. In a specificembodiment, vitamin E may be present in an amount of about 20 I.U. In aspecific embodiment, vitamin A may be in the form of beta carotene andpresent in an amount of about 1100 I.U. or about 660 μg. In a specificembodiment, vitamin C may be present in an amount of about 30 mg. In aspecific embodiment, vitamin B3 may be in the form of nicotinamide andpresent in an amount of about 15 mg. In a specific embodiment, iron maybe present in an amount of about 29 mg. In a specific embodiment, zincmay be present in an amount of about 25 mg. In a specific embodiment,copper may be present in an amount of about 2.0 mg. In a specificembodiment, magnesium may be present in an amount of about 20 mg. In aspecific embodiment, omega-3 fatty comprises DHA, and DHA may be presentin an amount of about 200 mg.

In one embodiment, the compositions may be provided in a gelcap dosageform. In a specific embodiment, the gelcap dosage form is a liquidgelcap dosage form.

One embodiment of the present invention may include providing vitamin,mineral, and omega-3 fatty acid supplementation to a patient in needthereof by administering compositions disclosed herein to the patient.In a specific embodiment, the patient may be a female human. In aspecific embodiment, the compositions may be administered to the femalehuman before pregnancy, during pregnancy, after pregnancy, whilebreast-feeding, or a combination thereof. In a specific embodiment, thecompositions are administered once daily to the patient.

In a specific embodiment, the methods may comprise administering acomposition comprising vitamin D in an amount of about 500 I.U. to about1500 I.U., iodine in an amount of about 75 μg to about 225 μg, vitaminB1 in an amount of about 0.8 mg to about 2.4 mg, vitamin B6 in an amountof about 1.2 mg to about 3.8 mg, vitamin B12 in an amount of about 6 μgto about 18 μg, vitamin B2 in an amount of about 0.9 mg to about 2.7 mg,vitamin B9 an amount of about 0.5 mg to about 1.5 mg, vitamin E in anamount of about 10 I.U. to about 30 I.U., vitamin A in an amount ofabout 550 I.U. to about 1650 I.U., vitamin C in an amount of about 15 mgto about 45 mg, vitamin B3 in an amount of about 7.5 mg to about 22.5mg, iron in an amount of about 14.5 mg to about 43.5 mg, zinc in anamount of about 12.5 mg to about 37.5 mg, copper in an amount of about1.0 mg to about 3.0 mg, magnesium in an amount of about 10 mg to about30 mg, and omega 3 fatty acids in an amount of about 100 mg to about 300mg.

In another specific embodiment, the methods may comprise administering acomposition comprising vitamin D in an amount of about 1000 I.U., iodinein an amount of about 150 μg, vitamin B1 in an amount of about 1.6 mg,vitamin B6 in an amount of about 2.5 mg, vitamin B12 in an amount ofabout 12 μg, vitamin B2 in an amount of about 1.8 mg, vitamin B9 in anamount of about 1.0 mg, vitamin E in an amount of about 20 I.U., vitaminA in an amount of about 1100 I.U., vitamin C in an amount of about 30mg, vitamin B3 in an amount of about 15 mg, iron in an amount of about29 mg, zinc in an amount of about 25 mg, copper in an amount of about2.0 mg, magnesium in an amount of about 20 mg, and omega 3 fatty acidscomprising DHA in an amount of about 200 mg.

DETAILED DESCRIPTION OF THE INVENTION

It is understood that the present invention is not limited to theparticular methodologies, protocols, fillers, and excipients, etc.,described herein, as these may vary. It is also to be understood thatthe terminology used herein is used for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention. It must be noted that as used herein and in theappended claims, the singular forms “a,” “an,” and “the” include theplural reference unless the context clearly dictates otherwise. Thus,for example, a reference to “a vitamin” is a reference to one or morevitamins and includes equivalents thereof known to those skilled in theart and so forth.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Specific methods, devices,and materials are described, although any methods and materials similaror equivalent to those described herein can be used in the practice ortesting of the present invention. All references cited herein areincorporated by reference herein in their entirety.

The term “disease state” as used herein, may comprise any state in whichone or more organs or components of an organism malfunction. The term“disease state” may refer to any deterioration of any component of apatient's body and specifically a human patient's body. The term“disease state” may refer to any deficiency of any compound necessaryfor the maintenance or function of any component of any organism. Theterm “disease state” may refer to any condition in which a body containstoxins, produced by microorganisms that infect the body or by body cellsthrough faulty metabolism or absorbed from an external source. “Diseasestates” may be adverse states caused by any diet, any virus, fungi orany bacteria. “Disease states” may comprise disorders associated withpregnant females such as, for example, osteomalacia and preeclampsia anddisorders associated with a fetus such as, for example, neural tubedefects and various fetal abnormalities. “Disease states” may compriseany pulmonary disorder such as, for example, bronchitis, bronchiectasis,atelectasis, pneumonia, diseases caused by inorganic dusts, diseasescaused by organic dusts, any pulmonary fibrosis, and pleurisy. “Diseasestates” may comprise any hematological/oncological disorder such as, forexample, anemia, hemophilia, leukemia, and lymphoma. A “disease state”may comprise any cancer such as, for example, breast cancer, lungcancer, prostate cancer, pancreatic cancer, liver cancer, stomachcancer, testicular cancer, ovarian cancer, skin cancer, cancer of thebrain, cancer of the mouth, cancer of the throat, and cancer of theneck. “Disease states” may comprise any disorder of the immune systemsuch as, for example, acquired immune deficiency syndrome (AIDS),AIDS-related complex, infection by any strain of any humanimmunodeficiency virus (HIV), and other viruses or pathogens such asbacteria, fungi and parasites. A “disease state” may comprise anycardiovascular disorder such as, for example, arterial hypertension,orthostatic hypotension, arteriosclerosis, coronary artery disease,cardiomyopathy, any arrhythmia, any valvular heart disease,endocarditis, pericardial disease, any cardiac tumor, any aneurysm, andany peripheral vascular disorder. “Disease states” may comprise anyhepatic/biliary disorder such as, for example, jaundice, hepaticsteatosis, fibrosis, cirrhosis, hepatitis, any hepatic granuloma, anyliver tumor, cholelithiasis, cholecystitis, and choledocholithiasis. A“disease state” may include a viral infection such as from HIV, herpesvirus (HSV-1 and HSV-2), the virus that causes vesicular stomatitis(VSV), measles virus, herpes viridae, human lymprotropic visusess,vesicular stomatitis virus, visna virus, cytomegalovirus, Epstein-Barrvirus, influenza virus, pneumonovirus, Sarcoma virus, Syncitial virusand Rubeola virus. A “disease state” may include a fungal infection suchas from Candida albicans and Giardia lamblia. A “disease state” mayinclude a bacterial infection such as from Staphylococcus,Corynebacerium, Bacillus, Listeria and Streptococcus bacteria, andinclude species such as Staphylococcus aureus, bacillus anthracis,Helicobacter pylori and, Listeria monocytogenes, and Streptococusagalactiae.

The term “patient,” as used herein, comprises any and all organisms andincludes the term “subject.” “Patient” may refer to a human or any otheranimal. “Patient” may also refer to a fetus.

The phrase “co-administration” refers to administration of two or morecompositions to a patient together, which includes administration atabout the same time or within a certain specific or desired time.

The phrase “chewable form” refers to any relatively soft compositionsthat are chewed in the mouth after oral administration, may have apleasant taste and mouthfeel, and may quickly break into smaller piecesand may begin to dissolve after chewing such that they can be swallowedsubstantially as a solution.

The phrase “dissolvable form” refers to any compositions that dissolveinto a solution in the mouth. Such compositions, in one embodiment, maydissolve within about 60 seconds or less after placement in the mouthwithout any chewing.

The term “mouthfeel” refers to non-taste-related aspects of thepleasantness experienced by a person while chewing or swallowing anutritional supplement. Aspects of mouthfeel include, for example andwithout limitation, the hardness and brittleness of a composition,whether the composition is chewy, gritty, oily, creamy, watery, sticky,easily dissolved, astringent, effervescent, and the like, and the size,shape, and form of the composition (tablet, powder, gel, etc.).

The phrase “pharmaceutically acceptable,” as used herein, refers tothose compounds, materials, compositions and/or dosage forms which are,within the scope of sound pharmaceutical/medical judgment, suitable foruse in contact with the tissues of human beings and animals withoutexcessive toxicity, irritation, allergic response, or other problem orcomplication, commensurate with a reasonable benefit/risk ratio. Thus,the phrase “pharmaceutically acceptable carriers,” as used herein,refers to such suitable compounds and materials defined above that maybe added to the dosage form to assist in satisfactory processing of thedosage form or provide desirable physical characteristics to the dosageform. For example, “pharmaceutically acceptable carriers” may include,but is not limited to, binders, diluents, lubricants, glidants,colorants, emulsifiers, disintegrants, starches, water, oils, alcohols,preservatives, and sugars. In another example, “pharmaceuticallyacceptable carriers” refers to dosage forms such as capsules, caplets,gel-caps used with, for example, the compositions of the presentinvention comprising or consisting of omega-3 fatty acids such asdocosahexaenoic acid (DHA). Thus, “pharmaceutically acceptable carriers”in gel-caps may be in for example, liquid or oil form, and may include afiller or other appropriate liquid vehicle and may be used with omega-3fatty acids such as docosahexaenoic acid (DHA) and their equivalents.

The phrase “swallowable form” refers to any compositions that typicallydo not or are not configured to readily dissolve when placed in themouth and may be swallowed whole, preferably without any, or withminimal, chewing or discomfort. Such compositions, in one embodiment,may have a shape containing no sharp edges and a smooth, uniform andsubstantially bubble free outer coating.

The term “dosage form,” as used herein, is the form in which the dose isto be administered to the subject or patient. The drug or supplement isgenerally administered as part of a formulation that includes nonmedicalagents. The dosage form has unique physical and pharmaceuticalcharacteristics. Dosage forms, for example, may be solid, liquid orgaseous. “Dosage forms,” may include for example, a capsule, tablet,caplet, gel caplet (gelcap), syrup, a liquid composition, a powder, aconcentrated powder, a concentrated powder admixed with a liquid, achewable form, a swallowable form, a dissolvable form, an effervescent,a granulated form, and an oral liquid solution. In a specificembodiment, the dosage form may be a gelcap.

The term “substantially free of added” as used herein, means free fromtherapeutically effective amounts of compounds when administered insuggested doses, but may include trace amounts of compounds innon-therapeutically effective amounts. For example, a composition of thepresent invention that included an inactive ingredient that is a salt orcompound including a mineral would still be substantially free of addedminerals. For example, trace amounts of titanium dioxide may beprovided. Titanium dioxide which is an effective opacifier in powderform, where it is employed as a pigment to provide whiteness and opacityto numerous pharmaceutical products.

As used herein, the terms “inactive,” “inert,” “excipient,” and/or“formulatory” refer to any compound that is an inactive ingredient of adescribed composition. The definition of “inactive ingredient” as usedherein follows that of the U.S. Food and Drug Administration, as definedin 21 C.F.R. 201.3(b)(8), which is any component of a drug product otherthan the active ingredient.

By “active ingredient,” then, includes any compound intended to furnishpharmacological activity or other direct effect in the diagnosis, cure,mitigation, treatment and/or prevention of disease or a condition. See21 C.F.R. 210.3(b)(7). Further, “active ingredients” include thosecompounds of the composition that may undergo chemical change during themanufacture of the composition and be present in the final compositionin a modified form intended to furnish an activity or effect. Id. Theseinclude the vitamins, minerals and nutrients of the compositions andkits of the present invention.

The term “administrable” defines a composition that is able to be givento a patient. Likewise, “administering” refers to the act of giving acomposition to a patient or otherwise making such composition availableto a patient or the patient taking a composition.

As used herein, the term “about,” when located before a dosage amount ordosage range of a specific ingredient, refers to an amount or rangeclosely above and/or closely below the stated amount or range that doesnot manifestly alter the therapeutic effect of the specific ingredientfrom the stated amount or range and is meant to encompass at least allequivalents of that amount.

The term “prenatal” supplementation includes optimizing specificnutrients before, during, and after the physiological processes ofpregnancy and lactation, which can have profound, positive, andcomprehensive impacts on the overall wellness of the developing andnewborn child as well as on the safety and health of the mother.

Proper nutrition is essential for maintaining health and preventingdiseases. Adequate nutrition is especially critical during, for example,nutritionally volatile or physiologically stressful periods such asthose including, by way of example and without limitation, pregnancy,lactation, or any disease state. Vitamin and mineral needs are almostuniversally increased throughout these periods. Increased needs duringphysiologically stressful states such as pregnancy, lactation or diseasestate may result from elevated metabolic demand, increased plasmavolume, increased quantities of circulating red blood cells, decreasedconcentrations of nutrients, and decreased concentrations ofnutrient-binding proteins such as, for example and without limitation,serum-ferritin, maltose-binding protein, lactoferrin, calmodulin,tocopheryl binding protein, riboflavin binding protein, retinol bindingprotein, transthyretin, high density lipoprotein-apolipoprotein A1,folic acid binding protein, and 25-hydroxyvitamin D binding protein.Lapido, 72 (Supp.) AMER. J. CLIN. NUTR. 280S-90S (2000). Optimizingspecific nutrients before, during, and after the physiological processesof pregnancy and lactation can have profound, positive, andcomprehensive impacts on the overall wellness of the developing andnewborn child as well as on the safety and health of the mother. Black,85 (Supp.) BRIT. J. NUTR. S193-97 (2001); Scholl et al., 146 AMER. J.EPIDEM. 134-41 (1997). Nutrients provided to a mother reach the fetus.Specifically, it is established that substrates for growth anddevelopment, for example, circulate within the same pathways that carrydrugs to and waste products from the fetus. Exchanges of materialbetween mother and fetus occur primarily in the placenta, where villicontaining fetal capillaries protrude into sinuses (intervillousspaces). Maternal arterial blood spurts into these spaces, then drainsinto maternal uterine veins to be returned to the maternal systemiccirculation. Solutes in maternal blood cross the epithelial cells andconnective tissue of the villi and the endothelium of the fetalcapillaries; these solutes are then carried to the fetus by placentalveins, which converge into the umbilical vein. THE MERCK MANUAL OFDIAGNOSIS AND THERAPY, (Mark H. Beers, M. D. et al., 18th ed. 2006).The, compositions, kits and methods of the present invention may thusprovide the means to optimize good health by utilizing vitamin, mineral,and nutritional supplementation. The compositions, kits and methods ofthe present invention may be administered to or directed to a subjectsuch as a human or any other organism.

The compositions, kits and methods of the present invention may includevitamin A. Vitamin A is involved in physiological processes that resultin cellular differentiation, cellular maturity, and cellularspecificity. Thus, vitamin A is an important component of a nutritionalsupplement for subjects in physiologically stressful states, such asthose caused by pregnancy, lactation or disease state. Zile et al.,131(3) J. NUTR. 705-08 (2001). Care should be taken, however, to avoidexcess. Indeed, supplemental vitamin A ingestion during pregnancy hasbeen shown in some studies to be teratogenic or deforming to human andanimal embryos. G B Mulder et al., 62(4) TERATOLOGY 214-26 (2000). Inone embodiment of the present invention, vitamin A may be in a form thatis a precursor (pro-vitamin) or metabolite of vitamin A that providessimilar nutritional value as vitamin A. For example, the pro-vitamin Acarotenoid, may be beta carotene. Beta carotene is converted to otherforms of vitamin A, specifically retinol, within the body as needed,thereby avoiding the risk of retinol toxicity. Mayne, FASEB J 10:690-701(1996). In a specific embodiment, vitamin A may be in one or more of theforms of retinol acetate (also known as retinyl acetate or vitamin Aacetate), retinol (vitamin A alcohol), retinol palmitate (also known asretinyl palmitate or vitamin A palmitate), retinoic acid (tretinoin),retinal, beta-cryptoxanthin, alpha-carotene, beta-carotene,gamma-carotene, and provitamin A carotenoids.

In a specific embodiment, vitamin A may be in the form of beta caroteneas beta carotene also has powerful anti-oxidant properties. Antioxidantsare important during physiologically stressful events for numerousreasons. For example, lipid peroxidation has been associated with over200 disease processes. Rock et al., 96(7) J. AMER. DIET. ASSOC. 693-702(1996). Antioxidants are especially important during pregnancy becausein the first trimester, establishment of blood flow into theintervillous space is associated with a burst of oxidative stress. Theinability to mount an effective antioxidant defense against this burstresults in early pregnancy loss. Myatt & Cui, 122, HISTOCHEM. CELLBIOL., 369-82 (2004). Further, oxidative stress has been implicated inthe pathophysiology of preeclampsia, a toxemia of pregnancy. Llurba etal., 37(4) FREE RADIC. BIOL. MED. 557-70 (2004). Finally, oxidativestress during pregnancy plays an important role in fetal growth, andhealthy antioxidant levels are positively correlated with birth weightand length. Myatt & Cui; Lee et al., 58 EUR. J. CLIN. NUTR., 481-87(2004).

In a specific embodiment of the compositions, kits and methods of thepresent invention, vitamin A may be included in amounts ranging fromabout 550 IU to about 1650 IU. In another specific embodiment, vitamin Amay be included in amounts ranging from about 880 IU to about 1320 IU.In another specific embodiment, vitamin A may be included in amountsranging from about 990 IU to about 1210 IU. In another embodiment,vitamin A may be included in an amount of about 1100 IU.

In another specific embodiment, vitamin A may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin A may be in the form of betacarotene and may be included in the amount of about 1100 IU.Accordingly, in this example, “beta carotene in the amount of about 1100IU” would include 1000 IU of beta carotene and/or its equivalents andwould, for example, include a product having 1100 IU retinol acetateinstead of beta carotene.

In another specific embodiment of the compositions, kits and methods ofthe present invention, vitamin A in the form of beta carotene may beincluded in amounts ranging from about 550 IU to about 1650 IU. Inanother specific embodiment, vitamin A in the form of beta carotene maybe included in amounts ranging from about 880 IU to about 1320 IU. Inanother specific embodiment, vitamin A in the form of beta carotene maybe included in amounts ranging from about 990 IU to about 1210 IU. Inanother embodiment, vitamin A in the form of beta carotene may beincluded in an amount of about 1100 IU. In another specific embodimentof the compositions, kits and methods of the present invention, vitaminA may be included in the form of beta carotene and one or more forms ofvitamin A. In a specific embodiment, the compositions, kits and methodsof the present invention may include beta carotene and retinol. Inanother embodiment, the compositions, kits and methods of the presentinvention may include beta carotene and retinol acetate.

In another embodiment, vitamin A may be present in an amount determinedby a measure of mass, as opposed to International Units. OneInternational Unit (IU) of vitamin A is defined as the biologicalequivalent of about 0.6 μg of beta carotene, or about 0.3 μg of retinol.See REMINGTON, THE SCIENCE AND PRACTICE OF PHARMACY, page 1804(20^(th)ed 2000). Accordingly, 550 IU to about 1650 IU is the biologicalequivalent of about 330 μg to about 990 μg. In another example, about880 IU to about 1320 IU is the biological equivalent of about 528 μg toabout 792 μg. In another example, about 990 IU to about 1210 IU is thebiological equivalent of about 594 μg to about 726 μg. In anotherexample, 1100 IU is the biological equivalent of about 660 μg.

The compositions, kits and methods of the present invention may compriseor use one or more B-complex vitamins. This class of vitamins compriseswater-soluble nutrients generally not stored in the body. They playroles in a variety of biological processes critical to the health ofpregnant women, lactating women, and fetuses such as, for example, themetabolism of homocysteine. The B-complex vitamins that may be includedin the compositions, kits and methods of the present invention compriseone or more of vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitaminB9 and vitamin B12.

The compositions, kits and methods of the present invention may compriseor use vitamin B1. Vitamin B1 plays a role in carbohydrate metabolismand neural function. It is a coenzyme for the oxidative decarboxylationof alpha-ketoacids (e.g., alpha-ketoglutarate and pyruvate) and fortransketolase, which is a component of the pentose phosphate pathway.NATIONAL RESEARCH COUNCIL, RECOMMENDED DIETARY ALLOWANCES, page 125(10th ed. 1989) (hereinafter “RDA”). In another specific embodiment,vitamin B1 may be in one or more of the forms of thiamine, thiaminemonophosphate, thiamine diphosphate, thiamine triphosphate, acetiamine,allithiamine, prosultiamine and S-acyl derivatives of thiamine such asbenfotiamine, fursultiamine and salts and esters thereof.

In another specific embodiment, vitamin B1 may be included in amountsranging from about 0.8 mg to about 2.4 mg. In another specificembodiment, vitamin B1 may be included in amounts ranging from about 1.3mg to about 1.9 mg. In another specific embodiment, vitamin B1 may beincluded in amounts ranging from about 1.4 mg to about 1.75 mg. Inanother embodiment, vitamin B1 may be included in an amount of about 1.6mg.

In another specific embodiment, vitamin B1 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B1 may be in the form of thiaminemononitrate and may be included in the amount of about 1.6 mg.Accordingly, in this example, “thiamine mononitrate in the amount ofabout 1.6 mg” would include 1.6 mg of thiamine mononitrate and/or itsequivalents and would, for example, include a product having 1.6 mgallithiamine instead of thiamine mononitrate.

The compositions, kits and methods of the present invention may compriseor use vitamin B2. Vitamin B2 is a component of two flavin coenzymes,flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Theseflavoenzymes are involved in a number of oxidation-reduction reactionsincluding the conversion of pyridoxine and niacin. RDA, supra at 132.Flavoenzymes also play a role in a number of metabolic pathways such asamino acid deamination, purine degradation and fatty acid oxidation andthus help to maintain carbohydrate, amino acid and lipid metabolism.

In a specific embodiment, vitamin B2 may be in one or more of the formsof flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD),riboflavin (also known as7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavinderivatives such as riboflavin-5′-monophosphate,riboflavin-5′-monobutyrate and riboflavin-5′-monopalmitate. In aspecific embodiment of the present invention, vitamin B2 may be includedin the form of riboflavin.

In another specific embodiment, vitamin B2 may be included in amountsranging from about 0.9 mg to about 2.7 mg. In another specificembodiment, vitamin B2 may be included in amounts ranging from about 1.5mg to about 2.2 mg. In another specific embodiment, vitamin B2 may beincluded in amounts ranging from about 1.6 mg to about 2 mg. In anotherembodiment, vitamin B2 may be included in an amount of about 1.8 mg.

In another specific embodiment, vitamin B2 in the form of riboflavin maybe included in amounts ranging from about 0.9 mg to about 2.7 mg. Inanother specific embodiment, vitamin B2 in the form of riboflavin may beincluded in amounts ranging from about 1.5 mg to about 2.2 mg. Inanother specific embodiment, vitamin B2 in the form of riboflavin may beincluded in amounts ranging from about 1.6 mg to about 2 mg. In anotherembodiment, vitamin B2 in the form of riboflavin may be included in anamount of about 1.8 mg.

In another specific embodiment, vitamin B2 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B2 may be in the form of riboflavinand may be included in the amount of about 1.8 mg. Accordingly, in thisexample, “riboflavin in the amount of about 1.8 mg” would include 1.8 mgof riboflavin and/or its equivalents and would, for example, include aproduct having 1.8 mg flavin mononucleotide instead of riboflavin.

The compositions, kits and methods of the present invention may compriseor use vitamin B3. Vitamin B3, or “niacin” is the common name for twocompounds: nicotinic acid (also called niacin) and niacinamide (alsocalled nicotinamide). Vitamin B3 is particularly important formaintaining healthy levels and types of fatty acids. It is also requiredfor the synthesis of pyroxidine, riboflavin, and folic acid. RDA, supraat 137. Administration of vitamin B3 also may effect a reduction intotal cholesterol (LDL) and very low density lipoprotein (VLDL) levelsand an increase in high density lipoprotein (HDL) cholesterol levels.Nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) areactive coenzymes of niacin. These coenzymes are involved in numerousenzymatic reactions such as glycolysis, fatty acid metabolism, andsteroid synthesis. Henkin et al., 91 AM. J. MED. 239-46 (1991). In aspecific embodiment, vitamin B3 may in the forms of niacin (nicotinicacid or pyridine-3-carboxylic acid), and nicotinamide (niacinamide) andsalts and esters thereof. In a specific embodiment of the presentinvention, vitamin B3 may be included in the form of nicotinamide. Inanother specific embodiment, the present invention may include anequivalent molar amount of niacin.

In another specific embodiment, vitamin B3 may be included in amountsranging from about 7.5 mg to about 22.5 mg. In another specificembodiment, vitamin B3 may be included in amounts ranging from about 12mg to about 18 mg. In another specific embodiment, vitamin B3 may beincluded in amounts ranging from about 13.5 mg to about 16.5 mg. Inanother embodiment, vitamin B3 may be included in an amount of about 15mg.

In another specific embodiment, vitamin B3 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B3 may be in the form ofnicotinamide and may be included in the amount of about 15 mg.Accordingly, in this example, “nicotinamide in the amount of about 15mg” would include 15 mg of nicotinamide and/or its equivalents andwould, for example, include a product having 15 mg niacin instead ofnicotinamide.

In another specific embodiment, vitamin B3 in the form of nicotinamidemay be included in amounts ranging from about 7.5 mg to about 22.5 mg.In another specific embodiment, vitamin B3 in the form of nicotinamidemay be included in amounts ranging from about 12 mg to about 18 mg. Inanother specific embodiment, vitamin B3 in the form of nicotinamide maybe included in amounts ranging from about 13.5 mg to about 16.5 mg. Inanother embodiment, vitamin B3 in the form of nicotinamide may beincluded in an amount of about 15 mg.

The compositions, kits and methods of the present invention may compriseor use vitamin B6. The administration of vitamin B6 may reduce thelevels of homocysteine. Bostom et al., 49 KIDNEY INT. 147-52 (1996). Theactive forms of vitamin B6, pyridoxal-5′-phosphate (PLP) andpyridoxamine-5′-phosphate, are coenzymes for numerous enzymes and assuch, are important for gluconeogenesis, niacin formation, anderythrocyte metabolism. RDA, supra at 142-43. Vitamin B6 is a coenzymefor both cystathionine synthase and cystathionase, enzymes that catalyzethe formation of cysteine from methionine. Homocysteine is anintermediate in this process and elevated levels of plasma homocysteineare recognized as a risk factor for both vascular disease (Robinson etal., 94 CIRCULATION 2743-48 (1996)) and neural tube defects (Locksmith &Duff, 91 OBSTET. GYNECOL. 1027-34 (1998)). In a specific embodiment ofthe present invention, vitamin B6 may be included in the forms ofpyridoxine, 3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine,5′-deoxypyridoxal, 2-demethylpyridoxal(2-norpyridoxal),2-propyl-2-norpyridoxal (2′-ethylpyridoxal), 6-methylpyridoxal,2′-hydroxypyridoxal (2-hydroxymethyl-2-demethylpyridoxal or2-hydroxymethyl-2-norpyridoxal), 4′-deoxypyridoxine 5′-phosphate,5′-methylpyridoxal-5′-phosphate, pyridoxal N-oxide 5′-phosphate,Pyridoxal, Pyridoxamine, Pyridoxine-5′-phosphate (PNP),pyridoxal-5′-phosphate (PLP) and pyridoxamine-5′-phosphate (PMP), andtheir salts and chelates thereof. In a specific embodiment of thepresent invention, vitamin B6 may be included in the form of pyridoxinehydrochloride.

In another specific embodiment, vitamin B6 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B6 may be in the form of pyridoxinehydrochloride and may be included in the amount of about 2.5 mg.Accordingly, in this example, “pyridoxine hydrochloride in the amount ofabout 2.5 mg” would include 2.5 mg of pyridoxine hydrochloride and/orits equivalents and would, for example, include a product having 2.5 mgpyridoxamine instead of pyridoxine hydrochloride.

In another specific embodiment, vitamin B6 may be included in amountsranging from about 1.2 mg to about 3.8 mg. In another specificembodiment, vitamin B6 may be included in amounts ranging from about 2.0mg to about 3.0 mg. In another specific embodiment, vitamin B6 may beincluded in amounts ranging from about 2.25 mg to about 2.75 mg. Inanother embodiment, vitamin B6 may be included in an amount of about 2.5mg.

The compositions, kits and methods of the present invention may compriseor use vitamin B9. Vitamin B9 is a generic name of a B-vitamin thatincludes multiple compounds with a general structure. For example,vitamin B9 encompasses the term folate, which itself is the generic namefor many different forms of this water-soluble vitamin (vitamin B9),which is essential for DNA synthesis and, hence, cell division. Simpsonet al., THE JOURNAL OF MATERNAL-FETAL AND NEONATAL MEDICINE ,Micronutrients and women of reproductive potential: required dietaryintake and consequences of dietary deficiency or excess. Part I—Folate,Vitamin B12, Vitamin B6, Epub 1-21, (2010). Indeed, folate encompassesnumerous compounds that for example, are based on a pteridine ring, anaminobenzoic acid and one or more glutamic acid residues. Id. Folic acid(pteroglutamic acid or PGA) is a synthetic form of folate, and the firstfolate synthesized and used as a supplement. Id. The term folates mayalso be used in the generic sense to designate any members of the familyof pteroylglutamates, or mixtures of them, having various levels ofreduction of the pteridine ring, one-carbon substitutions and numbers ofglutamate residues. PURE & APPL. CHEM ., IUPAC-IUB Commission onBiochemical Nomenclature (CBN). Nomenclature and Symbols for Folic Acidand Related Compounds. Arch 59, No. 6: 833-836 (1987).

Vitamin B9, however, is not only defined by its structure, but also byits various functions. Indeed, vitamin B9 is essential for DNA synthesisand, hence, cell division and is required metabolically as a coenzyme inone-carbon transfer reactions. Simpson, supra. This vitamin hasdemonstrated the ability to prevent neural tube defects such as spinabifida caused by disturbed homocysteine metabolism. Vanderput et al.,EXP. BIOL. MED. 243-70 (2001); DeFalco et al., 27 CLIN. EXP. OBSTET.GYNECOL. 188-90 (2000); Eskes, 27 CLIN. EXP. OBSTET. GYNECOL. 157-67(2000); Locksmith & Duff, supra. Folic acid, a commonly used termsynonymous with vitamin B9, is known to reduce the risk of multiplediseases. Clinical trials definitively demonstrated the effectiveness offolic acid supplementation in reducing the number of neural tubedefects. Simpson et al., THE JOURNAL OF MATERNAL-FETAL AND NEONATALMEDICINE , Micronutrients and women of reproductive potential: requireddietary intake and consequences of dietary deficiency or excess. PartI—Folate, Vitamin B12, Vitamin B6, Epub 1-21, (2010). Indeed, folic acidsupplementation in reducing the risk of neural tube defects and othercongenital malformations is generally accepted. Pietrzik et al., CLINPHARMACOKINET 49 (8): 535-548 (2010). Furthermore, evidence isaccumulating to support a possible role of folic acid in the reductionin risk of other diseases, including dementia and certain types ofcancer. Id. Lastly, folate or folate derivative thereof that increaseblood folate levels, thereby reducing homocysteine levels, which is acommon way to measure vitamin B9 effectiveness. Id.

Thus, in a specific embodiment of the present invention, vitamin B9 mayinclude numerous forms. In a specific embodiment, vitamin B9 may beincluded in the form of folic acid. In another embodiment, vitamin B9may be included one or more of the forms of folic acid, folacin,metafolin, folate and/or one or more natural isomers of folate including(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-formyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,10-formyl-(6R)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamylderivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or apolyglutamyl derivative thereof and 5-formimino-(6S)-tetrahydrofolicacid or a polyglutamyl derivative thereof and the salts and estersthereof. In another embodiment, vitamin B9 may be in the form of afolate or folate derivative thereof that is eventually converted to5-methyl-tetrahydrofolic acid in the body and/or is absorbed into thebloodstream as 5-methyl-tetrahydrofolic acid. Folates, such as folicacid and folate, are eventually absorbed in the body and converted toL-5-methyl-tetrahydrofolic acid In another embodiment, vitamin B9 may bein the form of a folate or folate derivative thereof that increasesblood folate levels, thereby reducing homocysteine levels.

In another embodiment, vitamin B9 may be in the form of folate orreduced folates with various salts. In a specific embodiment, the folateand reduced folate are selected from the group consisting ofD-glucosamine-folate, D-galactosamine-folate, D-glucosamine(6R,S)-tetrahydrofolate, D-glucosamine (6S)-tetrahydrofolate,D-glucosamine (6R)-tetrahydrofolate; D-galactosamine (6R,S)-tetrahydrofolate, D-galactosamine (6S)-tetrahydrofolate,D-galactosamine (6R)-tetrahydrofolate; D-glucosamine 5-methyl-(6R,S)-tetrahydrofolate, D-glucosamine 5-methyl-(6S)-tetrahydrofolate,D-glucosamine 5-methyl-(6R)-tetrahydrofolate; D-galactosamine5-methyl-(6R, S)-tetrahydrofolate, D-galactosamine5-methyl-(6S)-tetrahydrofolate, and D-galactosamine5-methyl-(6R)-tetrahydrofolate.

In another specific embodiment, vitamin B9 may be included in amountsranging from about 0.5 mg to about 1.5 mg. In another specificembodiment, vitamin B9 may be included in amounts ranging from about 0.8mg to about 1.2 mg. In another specific embodiment, vitamin B9 may beincluded in amounts ranging from about 0.9 mg to about 1.1 mg. Inanother embodiment, vitamin B9 may be included in an amount of about 1.0mg.

In another specific embodiment, vitamin B9 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B9 may be in the form folic acid andmay be included in the amount of about 1.0 mg. Accordingly, in thisexample, “folic acid in the amount of about 1.0 mg” would include 1.0 mgof folic acid and/or its equivalents and would, for example, include aproduct having 1.0 mg 5-methyl-(6S)-tetrahydrofolic acid instead offolic acid.

In a specific embodiment, vitamin B9 may be in the form of folic acid.In another specific embodiment, vitamin B9 in the form of folic acid maybe included in amounts ranging from about 0.5 mg to about 1.5 mg. Inanother specific embodiment, vitamin B9 in the form of folic acid may beincluded in amounts ranging from about 0.8 mg to about 1.2 mg. Inanother specific embodiment, vitamin B9 in the form of folic acid may beincluded in amounts ranging from about 0.9 mg to about 1.1 mg. Inanother embodiment, vitamin B9 in the form of folic acid may be includedin an amount of about 1.0 mg.

The compositions, kits and methods of the present invention may compriseor use vitamin B12. Vitamin B12 can be converted to the activecoenzymes, methylcobalamin and 5′-deoxyadenosylcobalamin. Thesecoenzymes are necessary for folic acid metabolism, conversion ofcoenzyme A and myelin synthesis. Methylcobalamin also catalyzes thedemethylation of a folate cofactor which is involved in DNA synthesis. Alack of demethylation may result in folic acid deficiency. RDA, supra at159-160. Deoxyadenosylcobalamin is the coenzyme for the conversion ofmethylmalonyl-CoA to succinyl-CoA, which plays a role in the citric acidcycle. Cobalamin, along with pyridoxine and folic acid, also areimplicated in the proper metabolism of homocysteine, a breakdown productof the amino acid methionine, which is correlated with an increased riskof heart disease due to its negative effects on endothelial function. Ina specific embodiment of the present invention, vitamin B12 may be inone or more of the forms of cobalamin, methylcobalamin,5′-deoxyadenosylcobalamin (adenosylcobalamin or cobamamide),cyanocobalamin, hydroxycobalamin and mecobalamin.

In another specific embodiment, vitamin B12 may be included in amountsranging from about 6 μg to about 18 μg. In another specific embodiment,vitamin B12 may be included in amounts ranging from about 9.6 μg toabout 14.4 μg. In another specific embodiment, vitamin B12 may beincluded in amounts ranging from about 10.8 μg to about 13.2 μg. Inanother embodiment, vitamin B12 may be included in an amount of about 12μg.

In another specific embodiment, vitamin B12 may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin B12 may be in the formcyanocobalamin and may be included in the amount of about 12 μg.Accordingly, in this example, “cyanocobalamin in the amount of about 12μg” would include 12 μg of cyanocobalamin and/or its equivalents andwould, for example, include a product having 12 μg methylcobalamininstead of cyanocobalamin.

The compositions, kits and methods of the present invention may compriseor use vitamin C. The major biochemical role of water-soluble vitamin Cis as a co-substrate in metal catalyzed hydroxylations. Like betacarotene, vitamin C has antioxidant properties. It interacts directlywith superoxide hydroxyl radicals and singlet oxygen, and also providesantioxidant protection for folate and vitamin E, keeping vitamin E inits most potent form. Vitamin C may afford protective effects againstpreeclampsia by participating in the scavenging of free radicals.Indeed, significantly lower levels of vitamin C have been observed inpreeclamptic women than in controls. Woods et al., 185(1) AM. J. OBSTET.GYNECOL. 5-10 (2001); Kharb, 1 EURO. J. OBSTET. GYNECOL. REPRO. BIOL.37-39 (2000); Milczarek et al., 210 MOL. CELL BIOCHEM. 65-73 (2000).Vitamin C also enhances the absorption of iron. RDA, supra at 115. Inaddition, vitamin C is required for collagen synthesis, epinephrinesynthesis, and bile acid formation. Moreover, vitamin C has beenimplicated in inhibiting atherosclerosis by being present inextracellular fluid of the arterial wall and potentiating nitric oxideactivity, thus normalizing vascular function. In a specific embodimentof the present invention, vitamin C may be included in the forms ofascorbic acid, ascorbates (calcium or sodium ascorbate), dehydroascorbicacid and salts, ascorbyl palmitate, ascorbyl phosphates and salts (suchas sodium or magnesium ascorbyl phosphate), ascorbyl tetraisopalmitate,tetrahexyldecyl ascorbate, ascorbyl sulfates and salts, acylatedascorbic acid derivatives (such as6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids),6-bromo-6-deoxy-L-ascorbic acid, and ascorbate salts. In a specificembodiment, vitamin C may be included in the form of ascorbic acid.

In another specific embodiment, vitamin C may be included in amountsranging from about 15 mg to about 45 mg. In another specific embodiment,vitamin C may be included in amounts ranging from about 24 mg to about36 mg. In another specific embodiment, vitamin C may be included inamounts ranging from about 27 mg to about 33 mg. In another embodiment,vitamin C may be included in an amount of about 30 mg.

In another specific embodiment, vitamin C may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin C may be in the form ascorbic acidand may be included in the amount of about 30 mg. Accordingly, in thisexample, “ascorbic acid in the amount of about 30 mg” would include 30mg of ascorbic acid and/or its equivalents and would, for example,include a product having 30 mg ascorbyl palmitate instead of ascorbicacid.

In another specific embodiment, vitamin C in the form of ascorbic acidmay be included in amounts ranging from about 15 mg to about 45 mg. Inanother specific embodiment, vitamin C in the form of ascorbic acid maybe included in amounts ranging from about 24 mg to about 36 mg. Inanother specific embodiment, vitamin C in the form of ascorbic acid maybe included in amounts ranging from about 27 mg to about 33 mg. Inanother embodiment, vitamin C in the form of ascorbic acid may beincluded in an amount of about 30 mg.

The compositions, kits and methods of the present invention may compriseor use vitamin D. In another embodiment, the compositions and methods ofthe present invention may include a beneficially increasedsupplementation of vitamin D. Vitamin D is a fat-soluble “hormone like”substance important for the maintenance of healthy bones. This vitaminincreases the absorption of calcium and phosphorous from thegastrointestinal tract, and improves mineral resorption into bonetissue. The result of this physiological function is a correlationbetween adequate systemic levels in pregnancy and a long-lastingreduction in osteoporotic fractures throughout the lifespan of thenewborn. M F Holick, “Vitamin D,” in MODERN NUTRITION IN HEALTH ANDDISEASE, p. 313, M E Shils, J A Olsen and M. Shikeeds., Plea andFebiger, Philadelphia, Pa. (1994); M K Javaid et al., LANCET367(9504):36-43 (2006).

Moreover, recent research suggests that vitamin D has more positivephysiological effects than previous thought. Bischoff-Ferrari H A, 624ADV EXP MED BIOL. 55-71 (2008); Holick M F, 357 N. ENG. J. MED. 266-81,(2007); Parikin et al., 89(3) J CLIN ENDOCRINOL METAB. 1196-99 (2004).For example, it has recently been determined that vitamin D also has arole in the enhancement of vascular function, defense against cancer,immuno-competence, blood pressure regulation and possessing the abilityto enhance cellular insulin sensitivity in the human body. Due to theadditional roles that vitamin D plays in the human body, it has recentlybeen determined that higher daily vitamin D intake beyond currentrecommendations may be associated with better health outcomes.Bischoff-Ferrari H A, supra. Indeed, studies suggest increasing theserum level of 25-hydroxyvitamin D, a beneficial derivative of vitaminD, to a 30 ng/ml serum range. Id. A 30 ng/ml appears to be the mostadvantageous serum levels in recent studies reviewing patient bonemineral density (BMD), lower extremity function, dental health, risk offalls, admission to nursing home, fractures, cancer prevention andincident hypertension. Id.

Further, studies suggest that an intake of about 1000 IU of vitamin D3(cholecalciferol) per day for all adults may bring at least 50% of thepopulation up to the 30 ng/ml serum range for 25-hydroxyvitamin D. Id.Current nutritional supplements, however, do not provide a high enoughdosage for obtaining such a high serum level of 25-hydroxyvitamin D.Presently, the suggested daily amount of vitamin D, as stated by theU.S. Dietary Reference Intake for adequate intake (AI) of vitamin D forinfants, children and men and women aged 19-50 is 200 IU/day. Adequateintake increases to 400 IU/day for men and women aged 51-70 and up to600 IU/day past the age of 70. Id. Due to these studies, presentnutritional supplements may be insufficient to remedy the current U.S.and global epidemic related to vitamin D deficiency.

Indeed, research findings indicate vitamin D status during pregnancy ismore important than previous thought. Vitamin D's role continues toexpand in for example, infant immunity, neurodevelopment, birth weight,and incidence of asthma. Growing research findings regarding theimportance of this hormone-like compound is due, in large part, to thefact that vitamin D receptors have now been identified on nearly everytissue and cell in the human body. H F DeLuca et al., FASEB J15:2579-2585 (2001); D. Eyles et al., NEUROSCIENCE 118(3):641-653(2003); C A Mannion et al., CMAJ 174(9):1273-1277 (2006); B W Hollis etal., CMAJ 174(9):1287-1290 (2006); American Academy of Allergy, Asthmaand Immunology Annual Meeting, Miami, Fla. (March 2006). A nutritionalsupplement that includes a higher dosage amount of vitamin D, ascompared to present nutritional supplements and, specifically, prenatalsupplements, is therefore currently needed. Thus, one embodiment of thepresent invention includes compositions, kits and methods that provide abeneficial increased supplementation of vitamin D, specifically, forexample prenatal, pregnant or breast feeding women.

The vitamin D of the compositions and methods of the present inventionmay comprise vitamin D. In a specific embodiment of the presentinvention, vitamin D may be in one or more the forms of vitamin D3 (alsoknown as calciol or cholecalciferol or colecalciferol), vitamin D2 (alsoknown as calciferol, ergocalciol, ergocalciferol, ercalciol, Deltalin orViosterol), previtamin D2, ergosterol, calcitriol (also known as1,25-dihydroxycholecalciferol), 7-dehydrocholesterol, vitamin D1,vitamin D4 (also known as 22-dihydroergocalciferol,22,23-dihydroercalciol or (24S)-methylcalciol), vitamin D5 (also knownas (24S)-Ethylcalciol or sitocalciferol), 7-dehydrositosterol,Lumisterol, 25-hydroxyvitamin D, all steroids that exhibit thebiological activity of calciol, 25-fluorocalciol,(3S)-3-amino-3-deoxycalciol, 11α-acetoxycalciol, calcidiol (also knownas 25-hydroxycholecalciferol or calcifediol), ercalcitriol, calcitetrol,tacalciol (also known as tachysterol₃), (5E)-isocalciol (also known asisovitamin D3), Dihydroercalciol (also known as dihydrotachysterol3),(1S)-Hydroxycalciol (also known as 1α-hydroxycholecalciferol oralfacaleidol), (24R)-Hydroxycalcidiol (also known as24(R),25-dihydroxycholecalciferol), Ercalcidiol, Ercalcitriol,Ertacalciol, (5E)-(10S)-10,19-Dihydroercalciol (also known asdihydrotachysterol2), (6Z)-Tacalciol (also known as precalciferol orpre-vitamin D), and (22E)-(24R)-Ethyl-22,23-didehydrocalciol also knownas vitamin D6.

In one embodiment of the invention, vitamin D may be present in theamount ranging from about 400 IU to about 1600 IU. In anotherembodiment, vitamin D may be present in the amount ranging from about750 IU to about 1250 IU. In another embodiment, vitamin D is present inthe amount ranging form about 900 IU to about 1100 IU. In anotherembodiment, vitamin D is present in the amount of about 1000 IU.

In another specific embodiment, vitamin D may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin D may be in the form vitamin D3 andmay be included in the amount of about 1000 IU. Accordingly, in thisexample, “vitamin D3 in the amount of about 30 mg” would include 1000 IUof vitamin D3 and/or its equivalents and would, for example, include aproduct having 1000 IU mg vitamin D2 instead of vitamin D3.

In another embodiment of the present invention, the vitamin D of thecompositions, kits and methods of the present invention may be vitaminD3. In the body, vitamin D3 is produced when its precursor is exposed toultraviolet irradiation (e.g., sunlight) and then hydroxylated in theliver to form 25-hydroxyvitamin D3, the major form of vitamin D in thecirculation. This form of the vitamin may be hydroxylated again in thekidney, yielding 1,25 hydroxyvitamin D3, the most potent form of vitaminD. As noted above, vitamin D3 plays a role in the maintenance of calciumand phosphorus homeostasis, but it is also active in celldifferentiation and immune function.

In one embodiment of the invention, vitamin D in the form of vitamin D3may be present in the amount ranging from about 400 IU to about 1600 IU.In another embodiment, vitamin D in the form of vitamin D3 may bepresent in the amount ranging from about 750 IU to about 1250 IU. Inanother embodiment, vitamin D in the form of vitamin D3 may be presentin the amount ranging form about 900 IU to about 1100 IU. In anotherembodiment, vitamin D in the form of vitamin D3 may be present in theamount of about 1000 IU.

In another embodiment, vitamin D may be present in an amount determinedby a measure of mass, as opposed to International Units. OneInternational Unit (IU) of vitamin D is defined as the biologicalequivalent of about 0.025 μg of vitamin D3. See REMINGTON, THE SCIENCEAND PRACTICE OF PHARMACY, page 1800 (20^(th) ed 2000) (hereinafter,“Remington”). Accordingly, 400 IU to about 1600 IU is the biologicalequivalent of about 10 μg to about 40 μg. In another example, about 750IU to about 1250 IU is the biological equivalent of about 18.75 μg toabout 31.25 μg. In another example, about 900 IU to about 1100 IU is thebiological equivalent of about 22.5 μg to about 27.5 μg. In anotherexample, 1000 IU is the biological equivalent of about 25 μg.

The compositions, kits and methods of the present invention may compriseor use vitamin E. Vitamin E is a fat-soluble vitamin antioxidant foundin biological membranes where it protects the phospholipid membrane fromoxidative stress. Vitamin E inhibits the oxidation of unsaturated fattyacids by trapping peroxyl free radicals. It is also an antiatherogenicagent, and studies have demonstrated a reduced risk of coronary heartdisease with increased intake of vitamin E. Stampfer et al., 328 NEWENG. J. MED. 1444-49 (1993). In addition, vitamin E, like beta caroteneand vitamin C, may afford protective effects against preeclampsia byparticipating in the scavenging of free radicals. As with vitamin C,significantly lower levels of vitamin E have been observed inpreeclamptic women than in controls. Woods et al., AM J OBSTET GYNECOL,185(1):5-10 (2001); Kharb, EURO. J. OBSTET GYNECOL REPROD BIOL, 1:37-39(2000); Milczarek et al., MOL CELL BIOCHEM, 210:65-73 (2000). In aspecific embodiment of the present invention, vitamin E may be includedin one or more of the forms of alpha, beta, gamma, and delta tocopherolsin its natural or synthetic (dl) forms; alpha, beta, gamma, and deltatocotrienols in its natural or synthetic (dl) forms, dl-alpha tocopherylderivatives such as dl-alpha tocopheryl esters, dl-alpha-tocopherylacetate or succinate and d-alpha-tocopheryl acetate or dl-alphatocopheryl phosphates (such as Ester-E®). In a specific embodiment ofthe present invention, vitamin E may be included in the form ofd-alpha-tocopheryl acetate. In another specific embodiment, vitamin Emay be included in the form of an equivalent molar amount of d-alphatocopheryl succinate.

In another specific embodiment, vitamin E may be included in amountsranging from about 10 IU to about 30 IU. In another specific embodiment,vitamin E may be included in amounts ranging from about 15 IU to about25 IU. In another specific embodiment, vitamin E may be included inamounts ranging from about 18 IU to about 22 IU. In another embodiment,vitamin E may be included in an amount of about 20 IU.

In another specific embodiment, vitamin E may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, vitamin E may be in the formd-alpha-tocopheryl acetate and may be included in the amount of about 20IU. Accordingly, in this example, “d-alpha-tocopheryl in the amount ofabout 20 IU” would include 20 IU of d-alpha-tocopheryl and/or itsequivalents and would, for example, include a product having 20 IUalpha-tocotrienol instead of d-alpha-tocopheryl.

The compositions, kits and methods of the present invention may compriseor use iron. A primary function of iron is to carry oxygen to bodilytissues via the hemoglobin part of red blood cells. Supplemental intakeof iron is critical to preventing anemia, a disorder associated with avariety of physiological states including, for example, pregnancy.Bothwell, 72(Supp.) AM. J. CLIN. NUTR. 257S-64S (2000). Severe anemiamay have adverse effects upon a mother and a fetus. Specifically,significant depression of hemoglobin has been associated with poorpregnancy outcome. Black, supra; Sifakis & Pharmakides, 900 ANN. N.Y.ACAD. SCI. 125-36 (2000). The, compositions, kits and methods of thepresent invention may include iron in one or more of the forms ofelemental iron, in the form of a salt, chelated form, non-chelated form,chelated to an amino acid, carbonyl iron, ferrous gluconate, ferrousfumarate, polysaccharide iron complex, elemental polysaccharide iron,polysaccharide iron, ferrous (II)-bis-glycinate chelate, ferrous aspartoglycinate, ferrous bisglycinate, ferrous bisglycinate hydrochloride,ferrous bisglycinate, elemental ferrous bisglycinate, ferrous sulfate,ferronyl (micronized), as Iron Aid, iron protein succinylate, carbonyliron, Sumalate iron, Heme iron complex, as Ferrochel amino acid chelate,heme iron polypeptide as Proferrin-bovine source, as heme ironpolypeptide (bovine source) as sodium iron EDTA (Ferrazone), ferricammonium citrate, elemental iron, and ferric pyrophosphate.

In a specific embodiment of the present invention, iron may be includedin the form of polysaccharide iron complex. In another specificembodiment, iron may be included in the form of an equivalent molaramount of ferrous fumarate. In another specific embodiment, iron may beincluded in amounts ranging from about 14.5 mg to about 43.5 mg. Inanother specific embodiment, iron may be included in amounts rangingfrom about 21.6 mg to about 32.4 mg. In another specific embodiment,iron may be included in amounts ranging from about 26 mg to about 32 mg.In another embodiment, iron may be included in an amount of about 29 mg.

In another specific embodiment, iron may be included in specific rangesor amounts for each specific form. When provided in their specificforms, the provided numerical range or amount includes the amounts ofthe specific form and/or compounds that are equivalent to the specificform. For example, iron may be in the form polysaccharide iron complexand may be included in the amount of about 29 mg. Accordingly, in thisexample, “polysaccharide iron complex in the amount of about 29 mg”would include 29 mg of polysaccharide iron complex and/or itsequivalents and would, for example, include a product having 29 mgferrous fumarate instead of polysaccharide iron complex.

The compositions, kits and methods of the present invention may compriseor use iodine. Iodine provides nutritional benefits as it is anessential component of the thyroid hormones that are involved in theregulation of various enzymes and metabolic processes, such as thyroxineand triiodothyronine. Thyroid hormones play pivotal roles in metabolism.Consequences of deficiency (hypothyroidism) and excess (hyperthyroidism)are well-recognized clinically. Simpson et al., THE JOURNAL OFMATERNAL-FETAL AND NEONATAL MEDICINE , Micronutrients and women ofreproductive potential: required dietaryintake and consequences ofdietary deficiency or excess. Part II—Vitamin D, Vitamin A, Iron, Zinc,Iodine, Essential Fatty Acids, 1-2, epub online 2010. Indeed, iodinedeficiency disorders (IDD) include mental retardation, hypothyroidism,goiter, cretinism, and varying degrees of other growth and developmentalabnormalities which can be a result from inadequate thyroid hormoneproduction from lack of sufficient iodine. Further, iodine is animportant element in breast milk for infant nutrition. An adequateconcentration of iodine in breast milk is essential to provide foroptimal neonatal thyroid hormone stores and to prevent impairedneurological development in breast-fed neonates. In many countries ofthe world, low iodine content of the breast milk indicates less thanoptimum maternal and infant iodine nutrition. F. Azizi et al., CLINENDOCRINOL; 70(5):803-9 (2009). Iodine deficiency, is a major publichealth problem in nearly all countries, particularly for women duringpregnancy and lactation. The National Health and Nutrition Examinationsurvey data also found 14.9% of women aged 15-44 years and 6.9% ofpregnant women to have urinary iodine concentrations of only 50 mg/L,indicating iodine intake of less than 100 mg daily. Simpson, supra. TheAmerican Thyroid Association thus also recommends that women receive 150mg iodine supplements daily during pregnancy and during lactation, whichis often the upper limit for iodine dosing amounts in prenatalsupplements. Id. Regardless of such recommendations, iodine nutritionand supplementation is lacking. For example, in Europe, most women areiodine deficient during pregnancy, with less than 50% receiving iodinesupplementation; of 40 countries, only nine met the requirements ofiodised salt at the household level to be at least 90% of the DRI. Id.Iodine nutrition of women of childbearing age thus remains inadequateand an area worthy of public health concern. Id. A nutritionalsupplement that includes a higher dosage amount of iodine, as comparedto present nutritional supplements and, specifically, prenatalsupplements, is therefore currently needed. Thus, one embodiment of thepresent invention includes compositions, kits and methods that provide abeneficial increased supplementation of iodine, specifically, forexample prenatal, pregnant or breast feeding women.

In a specific embodiment, iodine may be in the forms of elementaliodine, iodized salt, Lugol's iodine, sodium iodide, potassium iodide,potassium iodate, nascent iodine, and Nano-Colloidal Detoxified Iodine.In another specific embodiment, iodine may be present in the amountsranging from about 75 μg to about 225 μg. In another embodiment, iodinemay be present in the amounts ranging from about 120 μg to about 180 μg.In another embodiment, iodine may be present in the amounts ranging fromabout 135 μg to about 165 μg. In another embodiment, iodine may bepresent in the amount of about 150 μg.

In another specific embodiment, iodine may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, iodine may be in the form potassium iodideand may be included in the amount of about 150 μg. Accordingly, in thisexample, “potassium iodide in the amount of about 150 μg” would include150 μg of potassium iodide and/or its equivalents and would, forexample, include a product having 150 μg Nano-Colloidal DetoxifiedIodine instead of potassium iodide.

The compositions, kits and methods of the present invention may compriseor use magnesium. Magnesium is found primarily in both bone and muscleand is important for over 300 different enzyme reactions. A primaryfunction of magnesium is to bind to phosphate groups in adenosinetriphosphate (ATP), thereby forming a complex that assists in thetransfer of ATP phosphate. Magnesium also functions within cells as amembrane stabilizer. Magnesium plays roles in nucleic acid synthesis,glycolysis, transcription of DNA and RNA, amino acid activation,membrane transport, transketolase reactions, and protein synthesis.James L. L. Groff et al., ADVANCED NUTRITION AND HUMAN METABOLISM 341(2d ed. 1996). It is also involved in the formation of cAMP, a cytosolicsecond messenger that plays a role in cell signaling mechanisms.Magnesium also functions both synergistically and antagonistically withcalcium in neuromuscular transmission. RDA, supra at 188. Specifically,magnesium is critical for the maintenance of electrochemical potentialsof nerve and muscle membranes and the neuromuscular junctiontransmissions, particularly important in the heart. Not surprisingly,magnesium deficiency is tied to cardiovascular disease and hypertension.Agus et al., 17 CRIT. CARE CLIN. 175-87 (2001). Indeed, oral magnesiumtherapy improves endothelial function in patients with coronary disease.Shechter et al., 102 CIRCULATION 2353-58 (2000).

Magnesium is available in a variety of salts and can be included in thecompositions, kits and methods of the present invention in eitherchelated or nonchelated form. In one specific embodiment of the presentinvention, magnesium may be included in the forms of elementalmagnesium, in the form of a salt, in a chelated form, in a non-chelatedform, magnesium acetate, magnesium carbonate, magnesium gluconate,magnesium chloride, magnesium citrate, magnesium silicate, magnesiumstearate, magnesium sulfate, magnesium oxide, and magnesium chelated toan amino acid (magnesium glycinate, magnesium aspartate).

In another specific embodiment, magnesium may be present in the amountsranging from about 10 mg to about 30 mg. In another embodiment,magnesium may be present in the amounts ranging from about 16 mg toabout 24 mg. In another embodiment, magnesium may be present in theamounts ranging from about 18 mg to about 22 mg. In another embodiment,magnesium may be present in the amount of about 20 mg.

In another specific embodiment, magnesium may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, magnesium may be in the form magnesium oxideand may be included in the amount of about 20 mg. Accordingly, in thisexample, “magnesium oxide in the amount of about 20 mg” would include 20mg of magnesium oxide and/or its equivalents and would, for example,include a product having 20 mg magnesium stearate instead of magnesiumoxide.

The compositions, kits and methods of the present invention may compriseor use zinc. Zinc plays a role in numerous metabolic activities such asnucleic acid production, protein synthesis, and development of theimmune system. There are more than 200 zinc metalloenzymes includingaldolase, alcohol dehydrogenase, RNA polymerase, and protein kinase C.Zima et al., 17 BLOOD PURIF. 182-86 (1999). Zinc stabilizes RNA and DNAstructures, forms zinc fingers in nuclear receptors, and is a componentof chromatin proteins involved in transcription and replication.Deficiencies of zinc during pregnancy have been shown to contribute tosevere fetal abnormalities. Srinivas et al., 68(6) INDIAN J. PEDIATR.519-22 (2001); Yang et al., 13(4) BIOMED. ENVIRON. SCI. 280-86 (2000);King, 71(Supp.) AM. J. CLIN. NUTR. 1334S-43S (2000). Indeed, therecommended daily allowance for zinc increases during pregnancy. Ahigher dose of zinc, however, is associated with causing nausea in somepatients. Thus, for pregnant women or other patients that are moresusceptible to nausea, a conservative amount of zinc that still providesadequate nutritional supplementation is desirable. Zinc is available inmany forms and may be included in the kits and methods of the presentinvention in chelated or nonchelated form.

In a specific embodiment of the present invention, zinc may be providedin one or more of the forms of elemental zinc, in the form of a salt, ina chelated form, in a non-chelated form, zinc acetate, zinc gluconate,zinc picolinate, zinc sulfate and zinc oxide. In a specific embodimentof the present invention, zinc may be included in the form of zincoxide. In another specific embodiment, zinc may be included in amountsranging from about 12.5 mg to about 37.5 mg. In another specificembodiment, zinc may be included in amounts ranging from about 20 mg toabout 30 mg. In another specific embodiment, zinc may be included inamounts ranging from about 22.5 mg to about 27.5 mg. In anotherembodiment, zinc may be included in an amount of about 25 mg.

In another specific embodiment, zinc may be included in specific rangesor amounts for each specific form. When provided in their specificforms, the provided numerical range or amount includes the amounts ofthe specific form and/or compounds that are equivalent to the specificform. For example, zinc may be in the form zinc oxide and may beincluded in the amount of about 25 mg. Accordingly, in this example,“zinc oxide in the amount of about 25 mg” would include 25 mg of zincoxide and/or its equivalents and would, for example, include a producthaving 25 mg zinc sulfate instead of zinc oxide.

The compositions, kits and methods of the present invention may compriseor use copper. Copper is an important component of the process of geneexpression. Additionally, one of copper's most vital roles is to helpform hemoglobin, which, as previously discussed, carries oxygen totissues via its iron component. In this respect copper plays a key rolein protecting against anemia. Further, deficiencies of copper may leadto neutropenia and bone abnormalities in pregnant and lactating women.Uauy et al., AMER J CLIN NUTR 67:952S-959S (Supp.) (1998). In addition,a fetus must accumulate copper at a rate of 50 mcg×kg−1×d−1 over thelatter half of pregnancy; any deficiency in accumulation may lead to lowbirth weight and protein-energy malnutrition. Id. Many forms of copperare known to those skilled in the art, including copper oxide (ReadeAdvanced Materials, Providence, R.I.). In a specific embodiment, coppermay be included in the forms of a salt, in a chelated form, in anon-chelated form, cupric oxide, copper sulfate, copper gluconate,copper citrate, cupric acetate, alkaline copper carbonate, and coppersalicylate.

In another specific embodiment, copper may be included in amountsranging from about 1.0 mg to about 3.0 mg. In another specificembodiment, copper may be included in amounts ranging from about 1.6 mgto about 2.4 mg. In another specific embodiment, copper may be includedin amounts ranging from about 1.8 mg to about 2.2 mg. In anotherembodiment, copper may be included in an amount of about 2.0 mg.

In another specific embodiment, copper may be included in specificranges or amounts for each specific form. When provided in theirspecific forms, the provided numerical range or amount includes theamounts of the specific form and/or compounds that are equivalent to thespecific form. For example, copper may be in the form copper oxide andmay be included in the amount of about 2.0 mg. Accordingly, in thisexample, “copper oxide in the amount of about 2.0 mg” would include 2.0mg of copper oxide and/or its equivalents and would, for example,include a product having 2.0 mg copper sulfate instead of copper oxide.

The compositions, kits and methods of the present invention may compriseor use omega-3 fatty acids. Omega-3 fatty acids play integral roles inphysiological mechanisms that serve to prevent, treat and/or alleviatethe occurrence or negative effects of some diseases and has shownmultiple health-promoting properties in adults. For example, omega-3fatty acids are linked to health benefits such as preventing theoccurrence of cancer, preventing the occurrence of heart disease, andare helpful in brain health and immune function. Indeed, omega-3 fattyacids include essential fatty acids linked to numerous health benefits,such as docahexaenoic acid (or docosahexaenoic acid, DHA),eicosapentaenoic acid (EPA) and α-linolenic acid (ALA). In anotherspecific embodiment, the compositions, kits and methods of the presentinvention may comprise or use Docahexaenoic acid (or docosahexaenoicacid, DHA). In another specific embodiment, the compositions, kits andmethods of the present invention may comprise or use eicosapentaenoicacid (EPA). In another specific embodiment, the compositions, kits andmethods of the present invention may comprise or use α-linolenic acid(ALA).

The omega-3 fatty acid DHA, a major component of fish oil, has beenshown to be of particular importance, especially during pregnancy or forlowering blood pressure. Indeed, studies suggest that DHA, but not EPA,reduce ambulatory blood pressure and heart rate in hyperlipidemic men.TA Mori et al., HYPERTENSION. 34:253-260 (1999). The results of thisstudy thus suggest that DHA is the principal fatty acid in fish and fishoils that is responsible for blood pressure and heart rate effects inhumans. Id.

Further, DHA is vital for optimal fetal and infant brain/cognitivedevelopment, as well as for normal brain function throughout life. F MRioux, O. Hernell et al., ACTA PAEDIATR 95(2):137-144 (2006). The sleeppatterns of infants born to mothers with higher plasma phospholipid DHAsuggest greater central nerve system maturity. S R Cheruku, C JLammi-Keefe et al., AM J CLIN NUTR 76:608-613, 2002. Additionally,children with Attention Deficit Hyperactivity Disorder (ADHD) have beenshown to have abnormal levels of DHA. EA Mitchell, M. Manku et al., CLINPEDIATR 26:406-411 (1986); L J Stevens, J R Burgess et al., PHYSIOLBEHAV 59:915-920 (1996). Studies have indicated a correlation betweenmaternal DHA intake and intelligence quotient in the child. The directcorrelation between brain development and systemic DHA status issecondary to the fact that DHA is taken up by the brain in preference toother fatty acids. Adequate DHA levels in pregnancy have also beencorrelated with optimizing the length of gestation and decreasing therisk of neurodevelopmental psychopathology. These critical findings haveprompted the National Institute of Health (NIH) to recommend thatpregnant women consume at least 300 mg of omega-3 fatty acids duringpregnancy. N. Neurenger et al., NUTR REV 44:285-294 (1986); G. Hornstraet al., AM J CLIN NUTR 71:285S-291S (2000); I B Helland et al.,PEDIATRICS 111:E39-E44 (2003); F. Facchinetti et al., EUR REV MEDPHARMACOL SCI 9(1):41-48 (2005); R K McNamara et al., PROSTAGLANDINSLEUKOT ESSENT FATTY ACIDS (29 Aug. 2006).

DHA is also important for the development of the infant retina andimproving the visual acuity of the infant. C A Francois, W E Connor etal., AM J CLIN NUTR 77:226-233 (2003). Preterm infants have a more rapiddevelopment of visual acuity if fed human milk or formula enriched withDHA, compared to standard formula. M H Jorgensen, K F Michaelsen et al.,LIPIDS 31(1):99-105 (1996). An increase in visual acuity has also beenobserved to develop more rapidly in term infants breast-fed from motherswhose diets are supplemented with DHA. Id.

In addition to the aforementioned benefit of DHA to the developingchild, this essential fatty acid has also shown multiplehealth-promoting properties in adults. These include anti-thrombotic,anti-inflammatory and anti-atherosclerotic activity, all of which reducethe risk of heart disease. M Laidlaw and B J Holub, AM J CLIN NUTR77:37-42 (2003). Inverse relationships have also been found betweensystemic levels of omega-3 fatty acids such as DHA and incidence andseverity of mood disorders and depression, including postpartumdepression. Therefore, introduction of omega-3 during pregnancy has adouble benefit, to both child and mother. F B Hu et al., JAMA287(14):1815-1821 (2002); C. Von Schacky et al., ANN INTERN MED130:554-562 (1999); G. Parker et al., AM J PSYCHIATRY 163(6):969-978(2006); S J Otto et al., PROSTAGLANDINS LEUKOT ESSENT FATTY ACIDS69(3):237-243 (2003).

For women, DHA is particularly useful in counteracting the progressionof breast cancer. Human breast cancer cells exposed to DHA exhibit anincrease in cell death by apoptosis. B A Stoll, BR J NUTR 87(3):193-198,2002. DHA also inhibits cyclooxygenase-2, which promotes mammarycarcinogenesis. Id. DHA supplementation during pregnancy has also beenshown to increase the length of gestation by about six days, helpingmothers carry to a healthy full term. C M Smuts et al., OBSTETRICS ANDGYNECOLOGY 101(3):469-479 (2003).

Intake of omega-3 fatty acids such as DHA not only leads to theirincorporation into cell membrane lipids (B A Stoll, BR J NUTR87(3):193-198 (2002)), but also storage in adipose tissue and secretionin breast milk. C A Francois, W E Connor et al., AM J CLIN NUTR77:226-233 (2003). Although the human body can derive a limited amountof DHA from another fatty acid known as alpha-linolenic acid, thisprocess is inefficient for optimal needs. A rich dietary source ofdirect DHA is fish. Id. However, some lactating women are vegetarians,have limited access to fish or simply do not like fish. A furtherproblem with encouraging increased fish intake in pregnancy is that mostspecies contain methyl mercury (MeHg) in various amounts. MeHg is apotent neurotoxin that can increase the risk of retarded cognitivedevelopment. This concern prompted both the United States EnvironmentalProtection Agency (2004) and the Food and Drug Administration (2001) toissue advisories recommending that pregnant women modify their fishconsumption. These recommendations have resulted in a reduced intake offish during pregnancy, thus helping to protect against fetal MeHgrelated harm. However, this has concurrently reduced maternal intake ofDHA. In fact, a recent dietary study of over 100 pregnant or nursingwomen in the United States showed an astonishingly low intake of DHA onaverage (60-80 mg/day), and a dangerously low percentage (<2) consumedthe aforementioned recommended intake of 300 mg/day of DHA as set forthby the NIH. JT Cohen et al., AM J PREV MED, 29:353-365 (2005); U.S.Department of Health and Human Services, U.S. Environmental ProtectionAgency, “What you need to know about mercury in fish and shellfish,”Report EPA-823-F-04-009 (March 2004); E. Oken et al., OBSTET GYNECOL102:346-351 (2003).

DHA may be obtained in solid form, such as in a whole-cell microbialproduct, or in liquid form, such as in an oil. An example of DHA in oilform is DHASCO®-T vegetable oil from micro-algae (Martek BiosciencesCorporation, Columbia, Md.). In a specific composition, the DHA isDHAgold®, life's DHA™ (DHASCO®), any Algae Oil, Krill Oil and/orvegetarian DHA.

In a specific embodiment of the present invention, the source of DHA maybe from one or more of animal, fish, plants, algae or microorganismproduction.

In another embodiment, the compositions, kits and methods of the presentinvention may include DHA derived from algae. DHA derived from algae, asopposed to being derived from fish oil, has numerous beneficial effects.First, the DHA from algae does not have the “fishy” smell that can comewith DHA from fish oil. Indeed, high doses of DHA from fish oil mayresult in the patient having an unappealing after taste or a slight“fishy” body odor or “fishy” odor on the patient's breath. Second, DHAderived from algae can be more easily regulated to assure consistencyand further remove the risk of added chemicals or other dangers. Forexample, DHA from algae would not have the risk of being tainted withmercury as opposed to DHA from fish oil. Thus, DHA from algae providespregnant women and neonate with DHA without this risk and dangers ofmercury. In a specific embodiment, the source of DHA may be from algaeoil. In another specific embodiment, the source of algae oil may be oneor more of microalgae Schizochytrium sp, microalgae Crypthecodiniumcohnii, microalgae Ulkenia sp. SAM2179, microalgae Schizochytriumlinacinum strain SC-1. In another specific embodiment the source of DHAmay be Martek Oil C53-O100.

In another specific embodiment, omega-3 fatty acids may be included inamounts ranging from about 100 mg to about 300 mg. In another specificembodiment, omega-3 fatty acids may be included in amounts ranging fromabout 160 mg to about 240 mg. In another specific embodiment, omega-3fatty acids may be included in amounts ranging from about 180 mg toabout 220 mg. In another embodiment, omega-3 fatty acids may be includedin an amount of about 200 mg.

In another specific embodiment, omega-3 fatty acids may be included inspecific ranges or amounts for each specific form. When provided intheir specific forms, the provided numerical range or amount includesthe amounts of the specific form and/or compounds that are equivalent tothe specific form. For example, omega-3 fatty acids may be in the formof DHA and may be included in the amount of about 200 mg. Accordingly,in this example, “DHA in the amount of about 200 mg” would include 200mg of DHA and/or its equivalents and would, for example, include aproduct having 200 mg EPA instead of DHA.

In another specific embodiment, omega-3 fatty acids may be in the formof DHA and may be included in amounts ranging from about 100 mg to about300 mg. In another specific embodiment, omega-3 fatty acids in the formof DHA may be included in amounts ranging from about 160 mg to about 240mg. In another specific embodiment, omega-3 fatty acids in the form ofDHA may be included in amounts ranging from about 180 mg to about 220mg. In another embodiment, omega-3 fatty acids in the form of DHA may beincluded in an amount of about 200 mg.

The compositions, kits and methods of the present invention may includeor use a combination of the included vitamins, nutrients and mineralsjust described. In a specific embodiment, the compositions, kits andmethods of the present invention may include vitamin D, iodine, vitaminB1, vitamin B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitaminE, vitamin A, vitamin C, iron, zinc, copper, magnesium, omega 3 fattyacids and one or more pharmaceutically acceptable carriers.

In another embodiment, the vitamins, nutrients and minerals may beincluded or used in any specific form just described. In a specificembodiment, the omega 3 fatty acids may be DHA.

In another embodiment, the compositions, kits and methods of the presentinvention may include or use a combination of the included vitamins,nutrients and minerals in the ranges or amounts just described.

In a specific embodiment, the compositions, kits and methods of thepresent invention may include or use vitamin D in an amount of about 500I.U. to about 1500 I.U., iodine in an amount of about 75 μg to about 225μg, vitamin B1 in an amount of about 0.8 mg to about 2.4 mg, vitamin B6in an amount of about 1.2 mg to about 3.8 mg, vitamin B12 in an amountof about 6 μg to about 18 μg, vitamin B2 in an amount of about 0.9 mg toabout 2.7 mg, vitamin B9 in an amount of about 0.5 mg to about 1.5 mg,vitamin E in an amount of about 10 I.U. to about 30 I.U., vitamin A inan amount of about 550 I.U. to about 1650 I.U., vitamin C in an amountof about 15 mg to about 45 mg, vitamin B3 in an amount of about 7.5 mgto about 22.5 mg, iron in an amount of about 14.5 mg to about 43.5 mg,zinc in an amount of about 12.5 mg to about 37.5 mg, copper in an amountof about 1.0 mg to about 3.0 mg, magnesium in an amount of about 10 mgto about 30 mg, and omega 3 fatty acids comprising DHA in an amount ofabout 100 mg to about 300 mg. In a specific embodiment, the compositions, kits and methods of the present invention may include or use vitaminD in an amount of about 1000 I.U., iodine in an amount of about 150 μg,vitamin B1 in an amount of about 1.6 mg, vitamin B6 in an amount ofabout 2.5 mg, vitamin B12 in an amount of about 12 μg, vitamin B2 in anamount of about 1.8 mg, vitamin B9 in an amount of about 1.0 mg, vitaminE in an amount of about 20 I.U., vitamin A in an amount of about 1100I.U., vitamin C in an amount of about 30 mg, vitamin B3 in an amount ofabout 15 mg, iron in an amount of about 29 mg, zinc in an amount ofabout 25 mg, copper in an amount of about 2.0 mg, magnesium in an amountof about 20 mg, and omega 3 fatty acids comprising DHA in an amount ofabout 200 mg.

In one embodiment of the present invention, vitamin D3, iodine, vitaminB1, vitamin B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitaminE, vitamin A, vitamin C, iron, zinc, copper, magnesium, and omega 3fatty acids may be provided in one composition. In a specificembodiment, the composition may be in the dosage form of a gelcap. Toensure that all such ingredients may be provided in one gelcapcomposition, various inactive ingredients and pharmaceuticallyacceptable carries may be added. In a specific embodiment, a wetting,stabilizing agent may be used for the gelcap composition, In a specificembodiment, the wetting or stabilizing agent is lecithin oil. In anotherspecific embodiment beeswax may be added. In another specificembodiment, soybean oil may be added.

In another embodiment, the present invention may comprise one or morecompositions in a kit. In a specific embodiment, the one or morecompositions may include or use a combination of the vitamins, nutrientsand minerals just described. In a specific embodiment, the one or morecompositions may collectively use or include vitamin D, iodine, vitaminB1, vitamin B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitaminE, vitamin A, vitamin C, iron, zinc, copper, magnesium, omega 3 fattyacids and one or more pharmaceutically acceptable carriers.

In a specific embodiment, the two compositions may collectively use orinclude vitamin D, iodine, vitamin B1, vitamin B6, vitamin B12, vitaminB2, vitamin B9, vitamin B3, vitamin E, vitamin A, vitamin C, iron, zinc,copper, magnesium, omega 3 fatty acids and one or more pharmaceuticallyacceptable carriers.

In a specific embodiment, the multiple compositions, kits and methods ofthe present invention may collectively include or use vitamin D in anamount of about 500 I.U. to about 1500 I.U., iodine in an amount ofabout 75 μg to about 225 μg, vitamin B1 in an amount of about 0.8 mg toabout 2.4 mg, vitamin B6 in an amount of about 1.2 mg to about 3.8 mg,vitamin B12 in an amount of about 6 μg to about 18 μg, vitamin B2 in anamount of about 0.9 mg to about 2.7 mg, vitamin B9 in an amount of about0.5 mg to about 1.5 mg, vitamin E in an amount of about 10 I.U. to about30 I.U., vitamin A in an amount of about 550 I.U. to about 1650 I.U.,vitamin C in an amount of about 15 mg to about 45 mg, vitamin B3 in anamount of about 7.5 mg to about 22.5 mg, iron in an amount of about 14.5mg to about 43.5 mg, zinc in an amount of about 12.5 mg to about 37.5mg, copper in an amount of about 1.0 mg to about 3.0 mg, magnesium in anamount of about 10 mg to about 30 mg, and omega 3 fatty acids comprisingDHA in an amount of about 100 mg to about 300 mg.

In a specific embodiment, the multiple compositions, kits and methods ofthe present invention may collectively include or use vitamin D in anamount of about 1000 I.U., iodine in an amount of about 150 μg, vitaminB1 in an amount of about 1.6 mg, vitamin B6 in an amount of about 2.5mg, vitamin B12 in an amount of about 12 μg, vitamin B2 in an amount ofabout 1.8 mg, vitamin B9 in an amount of about 1.0 mg, vitamin E in anamount of about 20 I.U., vitamin A in an amount of about 1100 I.U.,vitamin C in an amount of about 30 mg, vitamin B3 in an amount of about15 mg, iron in an amount of about 29 mg, zinc in an amount of about 25mg, copper in an amount of about 2.0 mg, magnesium in an amount of about20 mg, and omega 3 fatty acids comprising DHA in an amount of about 200mg

In a specific embodiment, active ingredients such as the vitamins,minerals and nutrients of the present invention, may be included inoverages. Adding overages of these compounds may be necessary to meetthe amounts claimed on the product label and product insert to ensurethat those recited amounts are met throughout the shelf life of theproduct. Indeed, because of US regulatory requirements that label valuesreflect minimum contents of these nutrients, deviations in actualnutrient content from label values are usually thought to tend towardoverages. Dwyer et al., ANAL BIOANAL CHEM, 389:37-46 (2007). In aspecific embodiment, one or more of the vitamins, minerals and nutrientsmay be included in the compositions and methods of the present inventionin overages of the recited, specific label amounts of about 100% toabout 150% of the label amount, although the overages are dependant onthe stability of each ingredient. For example, overages of vitamin D andvitamin B12 may be necessary due to the lack of stability of specificforms. In another example, 5-methyltetrahydrofolate, a form of vitaminB9, is degraded by light, temperature and may degrade during processingand storage. Overages may be larger for some vitamins—particularly thosethat are less stable and more likely to deteriorate with a long shelflife, those that have other functions (such as antioxidants) in theproduct itself; for minerals, excess amounts with large overages areprobably less likely because of their increased bulk and shelf lifestability. Dwyer et al., ANAL BIOANAL CHEM, 389:37-46 (2007).Accordingly, when overages are included for any specific activeingredient, at some point in time, these ingredients with overages willdegrade so that they fall within the amounts provided in the specificlabel. Thus, there is no literal difference between the amounts foractive ingredients that include overages, and those amounts listed onthe specific label. Furthermore, overages provide an equivalent efficacyof the active ingredient over the shelf life of the product.Accordingly, an active ingredient provided in overage amounts is aninsubstantial change and performs substantially the same function, insubstantially the same way, and leads to substantially the same resultas that same active ingredient in the amounts as provided on thespecific label.

In another embodiment, the nutritional supplements may include multiplevitamins, nutrients and minerals in one composition. Providing a singlecomposition multivitamin and multinutrient supplement is an appealingfeature because it improves patient compliance. Patients, andspecifically for example, pregnant patients, often have nausea, and mayhave difficulties taking multiple pills. A one pill or one compositionnutritional supplement that includes the beneficial vitamins, nutrientsand minerals in appropriate dosage amounts would thus be beneficial forimproving patient compliance in for example, pregnant women. In aspecific embodiment one or more of the compositions may be in the dosageform of a gelcap.

In another specific embodiment, the compositions, kits and methods ofthe present invention may be in the form of a liquid gelcap which mayconsist of a filler comprising one or more pharmaceutically activematerials dissolved or dispersed in an appropriate liquid vehicleencapsulated in a gelatin shell generally comprising gelatin togetherwith a plasticizer such as glycerin or sorbitol. The filler material maycomprise, for example, polyethylene glycols. See, for example, U.S. Pat.Nos. 4,780,316; 5,419,916; 5,641,512; and 6,589,536 which are expresslyincorporated by reference herein.

A liquid gelcap has numerous advantages. First, it retains many of theadvantages of consumer acceptance and is easier to swallow due to theouter coating being a soft and elastic gelatin shell. Also, liquidcompositions are well suited for encapsulation within a soft gelatinshell, creating flexibility that further assists in the capsule beingeasier to swallow. The active drug contained in the liquid form also hasadvantages in dispersing the drug to the active site. For example, theactive drug does not first have to dissolve in the gastrointestinaltract, thereby facilitating absorption of the pharmacologically activesubstance. See, for example, U.S. Pat. No. 6,689,382 which is expresslyincorporated by reference herein. Other formulations take advantage ofthe liquid form by creating a sustained release gelatin capsule, therebypermitting the delivery of the drug in a controlled fashion. See, forexample, U.S. Pat. Nos. 5,324,280 and 6,929,803, which are expresslyincorporated by reference herein. Many shell and fill formulations arediscussed in “Advances in Softgel Formulation Technology”, M. S. Patel,F. S. S. Morton and H. Seager, Manufacturing Chemists, July 1989; “SoftElastic Gelatin Capsules: A Unique Dosage Form”, William R. Ebert,Pharmaceutical Technology, October 1977; and “Soft gelatin capsules: asolution to many tableting problems”, H. Seager, PharmaceuticalTechnology, September 1985.

In a specific embodiment, the present invention may comprise kits orcompositions in the dosage form of a soft-gel gelcap. A soft-gel is aone-piece, sealed, soft gelatin shell that contains a solution, asuspension, or a semi-solid paste. Soft-gels are predominantly used tocontain liquids wherein the active ingredients are present in thedissolved or suspended state. Soft-gels have been widely known and usedfor many years and for a variety of purposes. Because soft-gels haveproperties that are quite different from two-piece, hard shell capsules,the soft-gels are capable of retaining a liquid fill material. Soft-gelsare often used to encapsulate consumable materials, including vitamins,dietary supplements, pharmaceuticals, and the like, in a liquid vehicleor carrier. Soft-gels are a unique dosage form that can provide distinctadvantages over more traditional dosage forms such as tablets,hard-shell capsules, and liquids. These advantages include patientcompliance and consumer preference, improved bioavailability, speed ofproduct development in many cases, shortened manufacturing time,enhanced drug stability due to less exposure of the active ingredient tooxygen, excellent dose uniformity, and product differentiation.

In another embodiment, the nutritional supplements may include multiplevitamins, nutrients and minerals in more than one composition. In aspecific embodiment, various active ingredients may be incorporated intomultiple compositions as a kit. In one example, fat soluble compoundssuch as omega 3 fatty acids, may be included in one composition, whereaswater soluble vitamins such as B-complex vitamins and vitamin C may beseparated into another composition. In another example, the multiplecompositions may be separated due to size or the large dosage amounts ofspecific ingredients. In another example, the nutritionalsupplementation of a multivitamin may not be adequate in onecomposition. Accordingly, all the active ingredients may be divided intoa total of two compositions, three compositions, four compositions andfive composition. In one embodiment, each composition may have equalamounts of each active ingredient. In another embodiment, compositionsmay have unequal amounts of various active ingredients, or merelysupplemental amounts of specific active ingredients.

In another specific embodiment, the composition, kits and methods may beused as a dietary supplement. In another embodiment, the composition,kits and methods may be used as a prescription prenatal vitamin. Inanother embodiment, the compositions, kits and methods of the presentinvention, may be administered to a patient, such as a woman duringpregnancy, prenatal or who is breast-feeding. In another embodiment, thecompositions, kits and methods of the present invention may be utilizedor administered, once a day, twice a day, three times a day, four timesa day and five times a day. When multiple compositions are provided in akit, the compositions may be co-administered at the same or administeredseparately.

The compositions, kits and methods of the present invention may be usedor utilized in one or more dosage forms. In a specific embodiment, thedosage form more be a capsule, tablet, caplet, gel caplet (gelcap),syrup, a liquid composition, a concentrated powder, and a concentratedpowder admixed with a liquid. The kits may comprise multiplecompositions utilizing multiple dosage forms.

The ingredients of the present invention may thus be combined into acomposition which may be in the form of capsule, tablet, caplet, gelcaplet (gelcap), syrup, a liquid composition, a concentrated powder, anda concentrated powder admixed with a liquid, and which may beadministered alone or in suitable combination with other components. Forexample, the composition of the present invention may be administered inone or more caplets or gel caps as practical for ease of administration.Each of the vitamins, nutrients and minerals is commercially available,and can be blended to form a single composition or can form multiplecompositions, which may be co-administered. In a specific embodiment oneor more of the compositions may be in the dosage form of a gelcap.

To prepare the compositions of the present invention, each of the activeingredients may be combined in intimate admixture with a suitablecarrier according to conventional compounding techniques. The carriermay take a wide variety of forms depending upon the form of thepreparation desired for administration, e.g., oral, sublingual, nasal,topical patch, or parenteral.

In preparing the composition in oral dosage form, any of the usual mediamay be utilized. For liquid preparations (e.g., suspensions, elixirs,and solutions), media containing, for example water, oils, alcohols,flavoring agents, preservatives, coloring agents and the like may beused. Pharmaceutical acceptable carriers such as starches, sugars,diluents, granulating agents, lubricants, binders, disintegrating agentsand the like may be used to prepare oral solids (e.g., powders, caplets,pills, tablets, capsules, and lozenges). Controlled release forms mayalso be used. Because of their ease in administration, caplets, tablets,pills, and capsules represent the most advantageous oral dosage unitform, in which case solid carriers are employed. If desired, tablets maybe sugar coated or enteric coated by standard techniques. All of thesepharmaceutical carriers and formulations are well known to those ofordinary skill in the art. See, e.g., WADE & WALLER, HANDBOOK OFPHARMACEUTICAL EXCIPIENTS (2nd ed. 1994).

In a specific mode of administration, the dosage forms, may beswallowable, chewable or dissolvable.

Swallowable compositions are well known in the art and are those that donot readily dissolve when placed in the mouth and may be swallowed wholewithout any chewing or discomfort. In a specific embodiment of thepresent invention the swallowable compositions may have a shapecontaining no sharp edges and a smooth, uniform and substantially bubblefree outer coating.

To prepare the swallowable compositions of the present invention, eachof the active ingredients may be combined in intimate admixture with asuitable carrier according to conventional compounding techniques. In aspecific embodiment of the swallowable compositions of the presentinvention, the surface of the compositions may be coated with apolymeric film. Such a film coating has several beneficial effects.First, it reduces the adhesion of the compositions to the inner surfaceof the mouth, thereby increasing the patient's ability to swallow thecompositions. Second, the film may aid in masking the unpleasant tasteof certain drugs. Third, the film coating may protect the compositionsof the present invention from atmospheric degradation. Polymeric filmsthat may be used in preparing the swallowable compositions of thepresent invention include vinyl polymers such as polyvinylpyrrolidone,polyvinyl alcohol and acetate, cellulosics such as methyl and ethylcellulose, hydroxyethyl cellulose and hydroxylpropyl methylcellulose,acrylates and methacrylates, copolymers such as the vinyl-maleic acidand styrene-maleic acid types, and natural gums and resins such as zein,gelatin, shellac and acacia Pharmaceutical carriers and formulations forswallowable compounds are well known to those of ordinary skill in theart. See generally, e.g., WADE & WALLER, HANDBOOK OF PHARMACEUTICALEXCIPIENTS (2nd ed. 1994).

Chewable compositions are those that have a palatable taste andmouthfeel, are relatively soft and quickly break into smaller pieces andbegin to dissolve after chewing such that they are swallowedsubstantially as a solution.

In order to create chewable compositions, certain ingredients should beincluded to achieve the attributes just described. For example, chewablecompositions should include ingredients that create pleasant flavor andmouthfeel and promote relative softness and dissolvability in the mouth.The following discussion describes ingredients that may help to achievethese characteristics.

Chewable compositions preferably have a pleasant or palatable flavor anda pleasant mouthfeel. A variety of ingredients can be included in thecompositions of the present invention to enhance mouthfeel.

In the chewable compositions of the present invention, sugars such aswhite sugar, corn syrup, sorbitol (solution), maltitol (syrup),oligosaccharide, isomaltooligosaccharide, sucrose, fructose, lactose,glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose,dextrose, polydextrose, dextrin, compressible cellulose, compressiblehoney, compressible molasses and mixtures thereof may be added toimprove mouthfeel and palatability. Further, by way of example andwithout limitation, fondant or gums such as gelatin, agar, arabic gum,guar gum, and carrageenan may be added to improve the chewiness of thecompositions. Fatty materials that may be included in the presentinvention include, by way of example and without limitation, vegetableoils (including palm oil, palm hydrogenated oil, corn germ hydrogenatedoil, castor hydrogenated oil, cotton-seed oil, olive oil, peanut oil,palm olein oil, and palm stearin oil), animal oils (including refinedoil and refined lard whose melting point ranges from 30° to 42° C.),Cacao fat, margarine, butter, and shortening.

Alkyl polysiloxanes (commercially available polymers sold in a varietyof molecular weight ranges and with a variety of different substitutionpatterns) also may be used in the present invention to enhance thetexture, the mouthfeel, or both of the chewable nutritional supplementcompositions described herein. By “enhance the texture” it is meant thatthe alkyl polysiloxane improves one or more of the stiffness, thebrittleness, and the chewiness of the chewable supplement, relative tothe same preparation lacking the alkyl polysiloxane. By “enhance themouthfeel” it is meant that the alkyl polysiloxane reduces the grittytexture of the supplement once it has liquefied in the mouth, relativeto the same preparation lacking the alkyl polysiloxane.

Alkyl polysiloxanes generally comprise a silicon and oxygen-containingpolymeric backbone with one or more alkyl groups pending from thesilicon atoms of the back bone. Depending upon their grade, they canfurther comprise silica gel. Alkyl polysiloxanes are generally viscousoils. Exemplary alkyl polysiloxanes that can be used in the swallowable,chewable or dissolvable compositions of the present invention include,by way of example and without limitation, monoalkyl or dialkylpolysiloxanes, wherein the alkyl group is independently selected at eachoccurrence from a C₁-C₆-alkyl group optionally substituted with a phenylgroup. A specific alkyl polysiloxane that may be used is dimethylpolysiloxane (generally referred to as simethicone). More specifically,a granular simethicone preparation designated simethicone GS may beused. Simethicone GS is a preparation which contains 30% simethiconeUSP. Simethicone USP contains not less than about 90.5% by weight(CH₃)₃—Si{OSi(CH₃)₂}CH₃ in admixture with about 4.0% to about 7.0% byweight SiO₂.

Chewable compositions should begin to break and dissolve in the mouthshortly after chewing begins such that the compositions can be swallowedsubstantially as a solution. The dissolution profile of chewablecompositions may be enhanced by including rapidly water-soluble fillersand excipients. Rapidly water-soluble fillers and excipients preferablydissolve within about 60 seconds of being wetted with saliva. Indeed, itis contemplated that if enough water-soluble excipients are included inthe compositions of the present invention, they may become dissolvablerather than chewable composition forms. Examples of rapidly watersoluble fillers suitable for use with the present invention include, byway of example and without limitation, saccharides, amino acids and thelike. Disintegrants also may be included in the compositions of thepresent invention in order to facilitate dissolution. Disintegrants,including permeabilizing and wicking agents, are capable of drawingwater or saliva up into the compositions which promotes dissolution fromthe inside as well as the outside of the compositions. Suchdisintegrants, permeabilizing and/or wicking agents that may be used inthe present invention include, by way of example and without limitation,starches, such as corn starch, potato starch, pre-gelatinized andmodified starches thereof, cellulosic agents, such as Ac-di-sol,montrnorrilonite clays, cross-linked PVP, sweeteners, bentonite,microcrystalline cellulose, croscarmellose sodium, alginates, sodiumstarch glycolate, gums, such as agar, guar, locust bean, karaya, pectin,Arabic, xanthan and tragacanth, silica with a high affinity for aqueoussolvents, such as colloidal silica, precipitated silica, maltodextrins,beta-cyclodextrins, polymers, such as carbopol, and cellulosic agents,such as hydroxymethylcellulose, hydroxypropylcellulose andhydroxyopropylmethylcellulose.

Finally, dissolution of the compositions may be facilitated by includingrelatively small particles sizes of the ingredients used.

In addition to those described above, any appropriate fillers andexcipients may be utilized in preparing the swallowable, chewable and/ordissolvable compositions of the present invention so long as they areconsistent with the objectives described herein. For example, binders,are substances used to cause adhesion of powder particles ingranulations. Such compounds appropriate for use in the presentinvention include, by way of example and without limitation, acacia,compressible sugar, gelatin, sucrose and its derivatives, maltodextrin,cellulosic polymers, such as ethylcellulose, hydroxypropylcellulose,hydroxypropylmethyl cellulose, carboxymethylcellulose sodium andmethylcellulose, acrylic polymers, such as insoluble acrylateammoniomethacrylate copolymer, polyacrylate or polymethacryliccopolymer, povidones, copovidones, polyvinylalcohols, alginic acid,sodium alginate, starch, pregelatinized starch, guar gum, polyethyleneglycol and others known to those of ordinary skill in the art.

Diluents also may be included in the compositions of the presentinvention in order to enhance the granulation of the compositions.Diluents can include, by way of example and without limitation,microcrystalline cellulose, sucrose, dicalcium phosphate, starches,lactose and polyols of less than 13 carbon atoms, such as mannitol,xylitol, sorbitol, maltitol and pharmaceutically acceptable amino acids,such as glycin, and their mixtures.

Lubricants are substances used in composition formulations that reducefriction during composition compression. Lubricants that may be used inthe present invention include, by way of example and without limitation,stearic acid, calcium stearate, magnesium stearate, zinc stearate, talc,mineral and vegetable oils, benzoic acid, poly(ethylene glycol),glyceryl behenate, stearyl futmarate, and others known to those ofordinary skill in the art.

Glidants improve the flow of powder blends during manufacturing andminimize composition weight variation. Glidants that may be used in thepresent invention include, by way of example and without limitation,silicon dioxide, colloidal or fumed silica, magnesium stearate, calciumstearate, stearic acid, cornstarch, talc and others known to those ofordinary skill in the art.

Colorants also may be included in the nutritional supplementcompositions of the present invention. As used herein, the term“colorant” includes compounds used to impart color to pharmaceuticalpreparations. Such compounds include, by way of example and withoutlimitation, FD&C Red No. 3, FD&C Red No. 20, FD&C Yellow No. 6, FD&CBlue No. 2, D&C Green No. 5, FD&C Orange No. 5, D&C Red No. 8, caramel,and ferric oxide, red and others known to those of ordinary skill in theart. Coloring agents also can include pigments, dyes, tints, titaniumdioxide, natural coloring agents, such as grape skin extract, beet redpowder, beta carotene, annato, carmine, tumeric, paprika and othersknown to those of ordinary skill in the art. It is recognized that nocolorant is required in the nutritional supplement compositionsdescribed herein.

If desired, the compositions of the present invention may be sugarcoated or enteric coated by standard techniques. The unit dose forms maybe individually wrapped, packaged as multiple units on paper strips orin vials of any size, without limitation. The swallowable, chewable ordissolvable compositions of the present invention may be packaged inunit dose, rolls, bulk bottles, blister packs and combinations thereof,without limitation.

The swallowable, chewable or dissolvable compositions of the presentinvention may be prepared using conventional methods and materials knownin the pharmaceutical art. For example, U.S. Pat. Nos. 5,215,754 and4,374,082 relate to methods for preparing swallowable compositions. U.S.Pat. No. 6,495,177 relates to methods to prepare chewable nutritionalsupplements with improved mouthfeel. U.S. Pat. No. 5,965,162, relates tokits and methods for preparing multi-vitamin comestible units whichdisintegrate quickly in the mouth, especially when chewed. Further, allpharmaceutical carriers and formulations described herein are well knownto those of ordinary skill in the art, and determination of workableproportions in any particular instance will generally be within thecapability of the person skilled in the art. Details concerning any ofthe excipients of the invention may be found in WADE & WALLER, HANDBOOKOF PHARMACEUTICAL EXCIPIENTS (2nd ed. 1994). AU active ingredients,fillers and excipients are commercially available from companies such asAldrich Chemical Co., FMC Corp, Bayer, BASF, Alexi Fres, Witco,Mallinckrodt, Rhodia, ISP, and others.

A specific embodiment of the present invention may comprise kits orswallowable compositions packaged in blister packs. Blister packs aspackaging for swallowable compositions are well known to those ofordinary skill in the art. Blister packs may be made of a transparentplastic sheet which as been formed to carry a matrix of depression orblisters. One or more swallowable compositions are received in eachdepression or blister. A foil or plastic backing is then adhered acrossthe plane of the sheet sealing the swallowable compositions in theirrespective blisters. Examples of materials used for the blister packsinclude, but are not limited to, aluminum, paper, polyester, PVC, andpolypropylene. Alternative materials are known to those of ordinaryskill in the art. To remove a swallowable composition, the depressionmaterial is pressed in and the composition is pushed through the backingmaterial. Multiple blister packs may be placed in an outer package,often a box or carton for sale and distribution.

Another specific embodiment of the present invention may comprise kitsor swallowable compositions packaged in bottles. The bottle may be glassor plastic in form with a pop or screw top cap. Bottle packaging forcompositions in swallowable form are well known to those of ordinaryskill in the art.

Additionally, the unit dose forms may be individually wrapped, packagedas multiple units on paper strips or in vials of any size, withoutlimitation. The swallowable, chewable or dissolvable compositions of theinvention may be packaged in unit dose, rolls, bulk bottles, blisterpacks and combinations thereof, without limitation.

Other objectives, features and advantages of the present invention willbecome apparent from the following specific examples. The specificexamples, while indicating specific embodiments of the invention, areprovided by way of illustration only. Accordingly, the present inventionalso includes those various changes and modifications within the spiritand scope of the invention that may become apparent to those skilled inthe art from this detailed description. The invention will be furtherillustrated by the following non-limiting examples.

Without further elaboration, it is believed that one skilled in the art,using the preceding description, can utilize the present invention tothe fullest extent. The following examples are illustrative only, andnot limiting of the remainder of the disclosure in any way whatsoever.

Example 1

A composition of the following formulation was prepared in gel-cap form,including the appropriate excipients, by standard methods known to thoseof ordinary skill in the art:

Vitamin A (Beta Carotene) 1100 IU Vitamin C 30 mg Vitamin D (Vitamin D3)1000 IU Vitamin E 20 IU Vitamin B1 1.6 mg Vitamin B2 (Riboflavin) 1.8 mgVitamin B3 (Niacinamide) 15 mg Vitamin B6 2.5 mg Vitamin B9 (Folic Acid)1 mg Vitamin B12 12 μg Iron 29 mg Magnesium 20 mg Zinc 25 mg Copper 2.0mg Iodine 150 μg DHA 200 mg

Example 2

In another example, various active ingredients may be incorporated intomultiple compositions as a kit. In this non-limiting example, a firstcomposition of the following formulation is prepared in caplet form,including the appropriate excipients, by standard methods known to thoseof ordinary skill in the art:

Vitamin A (Beta Carotene) 1100 IU Vitamin C 30 mg Vitamin D (Vitamin D3)1000 IU Vitamin E 20 IU Vitamin B1 1.6 mg Vitamin B2 (Riboflavin) 1.8 mgVitamin B3 (Niacinamide) 15 mg Vitamin B6 2.5 mg Vitamin B9 (Folic Acid)1 mg Vitamin B12 12 μg Iron 29 mg Magnesium 20 mg Zinc 25 mg Copper 2.0mg Iodine 150 μg

A second composition of the following formulation is prepared in gel-capform by standard methods known to those of ordinary skill in the art:

DHA 200 mg

Example 3

In another example, various active ingredients may be divided intomultiple compositions or a kit. In this non limiting example, the activeingredients of the composition of Example 1 may be divided into multiplecompositions or kits. In this non limiting example, a first compositionof the following formulation is prepared in gel-cap form, including theappropriate excipients, by standard methods known to those of ordinaryskill in the art:

Vitamin A (Beta Carotene) 550 IU Vitamin C 15 mg Vitamin D (Vitamin D3)500 IU Vitamin E 10 IU Vitamin B1 0.8 mg Vitamin B2 (Riboflavin) 0.9 mgVitamin B3 (Niacinamide) 7.5 mg Vitamin B6 1.25 mg Vitamin B9 (FolicAcid) 0.5 mg Vitamin B12 6.0 μg Iron 14.5 mg Magnesium 10 mg Zinc 12.5mg Copper 1.0 mg Iodine 75 μg DHA 100 mg

A second composition of the following formulation is prepared in gel-capform by standard methods known to those of ordinary skill in the art:

Vitamin A (Beta Carotene) 550 IU Vitamin C 15 mg Vitamin D (Vitamin D3)500 IU Vitamin E 10 IU Vitamin B1 0.8 mg Vitamin B2 (Riboflavin) 0.9 mgVitamin B3 (Niacinamide) 7.5 mg Vitamin B6 1.25 mg Vitamin B9 (FolicAcid) 0.5 mg Vitamin B12 6.0 μg Iron 14.5 mg Magnesium 10 mg Zinc 12.5mg Copper 1.0 mg Iodine 75 μg DHA 100 mg

Example 4

A study is undertaken to evaluate the effectiveness of the compositionsof the present invention in the treatment of patients. The objective ofthe study is to determine whether oral intake of the compositionsresults in an improvement of the nutritional status of patients withregard to the specific vitamins and minerals contained in theadministered compositions.

A double-blind, placebo controlled study is conducted over a six-monthperiod. A total of 120 subjects (60 pregnant women entering the secondtrimester of pregnancy and 60 lactating women), aged 20-35 years, arechosen for the study. An initial assessment of the nutritional status ofeach woman is conducted. Vitamin A and vitamin B6 are measured usinghigh performance liquid chromatography. Erythrocyte transketolaseactivity is used to measure vitamin B1 levels. Vitamin B2 levels aredetermined by assessment of erythrocyte glutathione reductase activity.Vitamin B3 levels are assessed by measuring urinary excretion ofN′methylnicotinamide and its pyridone. Vitamin B9 is measured byradioimmunoassay (RIA), specifically The Solid Phase No Biol Folic AcidKit (Diagnostic Products, Los Angeles, Calif.). Vitamin B12 is measuredby RIA using human intrinsic factor as a binder. Vitamin C levels aremeasured by spectrophotometric and colorimetric methods. Vitamin D ismeasured using an extraction double-antibody RIA (Dia Sorin, Inc.,Stillwater, Minn.). The peroxide hemolysis test is used to determinevitamin E status. Iron levels are measured using standardspectrophotometry. Iodine levels are measured by HPLC. Magnesium levelsare measured by absorbance of a magnesium chelate with xylid1 blue at660 nM. Zinc levels are assessed using flame atomic absorptionspectrometry (Perkins Elmer 460, Norwalk, Conn.). DHA is measured andquantified using gas chromatography procedures.

Additionally, total serum homocysteine levels are determined byextraction on the Multi-Prep® gravity series GVSA-100 column, a stronganion exchange gravity flow column, and measurement by gaschromatography/mass spectrometry. Biochemical Diagnostics, Austin, Tex.

The 120 subjects are separated into four separate groups of 30 women. Ina first group comprising only pregnant women and in a second groupcomprising only lactating women, each subject is administered one dosageform of the composition as described in Example 1 once a day. In a thirdgroup comprising only pregnant women and in a fourth group comprisingonly lactating women, each subject is administered one placebo dosageform once a day. Thus, dosage form administration occurs every 24 hours.No other nutritional supplements are taken by the subjects during theassessment period.

An assessment of the nutritional status of each woman is conductedutilizing the methods described above at one month intervals for a sixmonth period. The data is evaluated using multiple linear regressionanalysis and a standard t-test. In each analysis, the baseline value ofthe outcome variable is included in the model as a covariant. Treatmentby covariant interaction effects is tested by the method outlined byWeigel & Narvaez, 12 CONTROLLED CLINICAL TRIALS 378-94 (1991). If thereare no significant interaction effects, the interaction terms areremoved from the model. The regression model assumptions of normalityand homogeneity of variance of residuals are evaluated by inspection ofthe plots of residuals versus predicted values. Detection of thetemporal onset of effects is done sequentially by testing for thepresence of significant treatment effects at 1, 2, 3, 4, 5, and 6months, proceeding to the earlier time in sequence only when significanteffects have been identified at each later time period. Changes from thebaseline within each group are evaluated using paired t-tests. Inaddition, analysis of variance is performed on all baseline measurementsand measurable subject characteristics to assess homogeneity betweengroups. All statistical procedures are conducted using the StatisticalAnalysis System (SAS Institute Inc., Cary, N.C.). An alpha level of 0.05is used in all statistical tests.

An unexpected statistically significant improvement in the nutritionalstatus of vitamin, mineral, and nutrient levels measured is observed inthe treated subjects over the controls upon completion of the study.Specifically, homocysteine levels in women receiving supplements remainunelevated. Therefore, the study confirms that oral administration ofthe compositions of the present invention is effective in improving thenutritional status of patients. Other unexpected results relate to theobservation that the length of gestation is increased by approximatelysix days in women receiving supplements, due to DHA intake, and theirhomocysteine levels are not elevated, due to folic acid intake, leadingto a better prognosis regarding risk of neural tube defects in theirinfants.

Example 5

A study is undertaken testing supplementation of iodine, and vitamin D.A study is conducted over a three-month period. A total of 120 subjects(pregnant women entering the second trimester of, aged 20-35 years, arechosen for the study) An initial assessment of the nutritional status ofeach woman for iodine, and vitamin D is conducted as provided in Example4.

In the first group, each subject is administered 1 gelcap daily, withthe composition as described in Example 1. In the second group, eachsubject is administered 1 one caplet daily that includes the followingingredients in the listed amounts (control):

Vitamin A (acetate) 1100 IU Beta Carotene 600 IU Vitamin B₁ (thiaminemononitrate) 1.6 mg Vitamin B₂ (riboflavin) 1.8 mg Vitamin B₃(niacinamide) 15 mg Vitamin B₆ (pyridoxine hydrochloride) 2.5 mg VitaminB₉ (folic acid) 1000 μg Vitamin B₁₂ (cyanocobalamin) 5 μg Vitamin C(ascorbic acid) 60 mg Vitamin D (cholecalciferol) 400 IU Vitamin E(d-alpha-tocopheryl acetate) 30 IU Iron (polysaccharide complex) 29 mgMagnesium (magnesium oxide) 25 mg Zinc (zinc oxide) 15 mg

An assessment of nutritional status for each subject is measured atone-month intervals for a six month period. Specifically, in regard tovitamin D deficiency, the serum levels of 25-hydroxyvitamin D aremeasured to assess if they meet levels as high as 30 ng/ml or areincreasing towards a level of 30 ng/ml. The data is evaluated usingmultiple linear regression analysis and a standard students t-test. Ineach analysis the baseline value of the outcome variable is included inthe model as a covariant. Treatment by covariant interaction effects istested by the method outlined by Weigel & Narvaez, 12 CONTROLLEDCLINICAL TRIALS 378-94 (1991). If there are no significant interactioneffects, the interaction terms are removed from the model. Theregression model assumptions of normality and homogeneity of variance ofresiduals are evaluated by inspection of the plots of residuals versuspredicted values. Detection of the temporal onset of effects is donesequentially by testing for the presence of significant treatmenteffects at 16, 12, and 8 weeks, proceeding to the earlier time insequence only when significant effects have been identified at eachlater time period. Changes from the baseline within each group areevaluated using paired t-tests. In addition, analysis of variance isperformed on all baseline measurements and measurable subjectcharacteristics to assess homogeneity between groups. All statisticalprocedures are conducted using the Statistical Analysis System (SASInstitute Inc., Cary, N.C.). An alpha level of 0.05 is used in allstatistical tests.

A statistically significant improvement in the nutritional status ispreferably observed in the treated subjects who were administered thecomposition of Example 1 over treated subjects who are administered thecontrols. Specifically, in regard to vitamin D supplementation, thetested serum levels of 25-hydroxyvitamin D are preferably in the rangeof 30 ng/ml for treated subjects. Specifically, in regard to iodinecontent, serum levels show an increased level of iodide levels; whereasthe control shows not increased iodide serum level.

While specific embodiments of the present invention have been described,other and further modifications and changes may be made withoutdeparting from the spirit of the invention. All further and othermodifications and changes are included that come within the scope of theinvention as set forth in the claims. The disclosure of each publicationcited above is expressly incorporated by reference in its entirety tothe same extent as if each were incorporated by reference individually.

1. A method for improving a nutritional status in a prenatal, pregnantor breastfeeding patient, the method comprising: providing apharmaceutical composition in a single oral dosage form foradministration to a prenatal, pregnant or breastfeeding patient, thepharmaceutical composition consisting of: vitamin D in an amount ofabout 500 I.U. to about 1500 I.U., iodine in an amount of about 75 μg toabout 225 μg, vitamin B1 in an amount of about 0.8 mg to about 2.4 mg,vitamin B6 in an amount of about 1.2 mg to about 3.8 mg, vitamin B12,vitamin B2 in an amount of about 0.9 mg to about 2.7 mg, vitamin B9 inan amount of about 0.5 mg to about 1.5 mg, vitamin B3 in an amount ofabout 7.5 mg to about 22.5 mg, vitamin E in an amount of about 10 I.U.to about 30 I.U., vitamin A in an amount of about 550 I.U. to about 1650I.U., vitamin C, iron, zinc in an amount of about 12.5 mg to about 37.5mg, copper in an amount of about 1.0 mg to about 3.0 mg, magnesium in anamount of about 10 mg to about 30 mg, omega-3 fatty acids in an amountof about 100 mg to about 300 mg and one or more pharmaceuticallyacceptable carriers; and providing a daily dosage regimen foradministering the single oral dosage form to the patient to improve anutritional status in the patient.
 2. The method of claim 1, wherein thesingle oral dosage form is selected from the group consisting of: acapsule, tablet, caplet, gelcap, syrup, a liquid composition, a powder,a concentrated powder, a concentrated powder admixed with a liquid, achewable form, a swallowable form, a dissolvable form, an effervescent,a granulated form, and an oral liquid solution.
 3. The method of claim2, wherein the single oral dosage form is a gelcap.
 4. The method ofclaim 3, wherein the daily dosage regimen is one gelcap daily.
 5. Themethod of claim 1, wherein compliance with the daily dosage regimen inthe patient is improved over a 6 month period of administration.
 6. Themethod of claim 1, wherein the nutritional status of the patient isimproved after a 6 month period of administration.
 7. The method ofclaim 6, wherein the improvement in the nutritional status of thepatient is an improvement in at least one of the vitamin, mineral andnutrient levels of the patient.
 8. The method of claim 6, wherein theimprovement in the nutritional status of the patient is an unelevatedhomocysteine serum level in the patient.
 9. The method of claim 1,wherein said vitamin D is in the form selected from one or more of thegroup consisting of vitamin D3, vitamin D2, previtamin D2, ergosterol,calcitriol, 7-dehydrocholesterol, Vitamin D1, vitamin D4, vitamin,7-dehydrositosterol, Lumisterol, 25-hydroxyvitamin D, all steroids thatexhibit the biological activity of calciol, 25-fluorocalciol,(3S)-3-amino-3-deoxycalciol, 11α-acetoxycalciol, calcidiol,ercalcitriol, calcitetrol, tacalciol, (5E)-isocalciol, Dihydroercalciol,(1S)-Hydroxycalciol, (24R)-Hydroxycalcidiol, Ercalcidiol, Ercalcitriol,Ertacalciol, (5E)-(10S)-10,19-Dihydroercalciol, (6Z)-Tacalciol, and(22E)-(24R)-Ethyl-22,23-didehydrocalciol; wherein said vitamin B1 is inthe form selected from one or more of the group consisting of thiamine,thiamine mononitrate, thiamine monophosphate, thiamine diphosphate,thiamine triphosphate, acetiamine, allithiamine, prosultiamine andS-acyl derivatives of thiamine, including benfotiamine, fursultiamineand salts and esters thereof; wherein said vitamin A is in the formselected from one or more of the group consisting of retinol acetate,retinol, retinol palmitate, retinoic acid, retinal, beta-cryptoxanthin,alpha-carotene, beta-carotene, gamma-carotene, and provitamin Acarotenoids; wherein said vitamin B9 is in the form selected from one ormore of the group consisting of folic acid, folinic acid, folacin,metafolin, and/or one or more natural isomers of folate including(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,(6S,R)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-methyl-(6S,R)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5-formyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 10-formyl-(6R)-tetrahydrofolic acid or a polyglutamylderivative thereof, 5,10-methylene-(6R)-tetrahydrofolic acid or apolyglutamyl derivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acidor a polyglutamyl derivative thereof and5-formimino-(6S)-tetrahydrofolic acid or a polyglutamyl derivativethereof and their salts and esters thereof; wherein said vitamin B2 isin the form selected from one or more of the group consisting of flavinmononucleotide (FMN), flavin adenine dinucleotide (FAD), riboflavin(also known as 7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavinderivatives, including riboflavin-5′-monophosphate,riboflavin-5′-monobutyrate and riboflavin-5′-monopalmitate; wherein saidvitamin B3 is in the form selected from one or more of the groupconsisting of niacin, and nicotinamide and salts and esters thereof;wherein said vitamin B6 is in the form selected from one or more of thegroup consisting of pyridoxine,3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine, 5′-deoxypyridoxal,2-demethylpyridoxal(2-norpyridoxal), 2-propyl-2-norpyridoxal(2′-ethylpyridoxal), 6-methylpyridoxal, 2′-hydroxypyridoxal(2-hydroxymethyl-2-demethylpyridoxal or 2-hydroxymethyl-2-norpyridoxal),4′-deoxypyridoxine 5′-phosphate, 5′-methylpyridoxal-5′-phosphate,pyridoxal N-oxide 5′-phosphate, Pyridoxal, Pyridoxamine,Pyridoxine-5′-phosphate (PNP), pyridoxal-5′-phosphate (PLP) andpyridoxamine-5′-phosphate (PMP), and their salts and chelates thereof;wherein said vitamin B12 is in the form selected from one or more of thegroup consisting of cobalamin, methylcobalamin,5′-deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin andmecobalamin; wherein said vitamin E is in the form selected from one ormore of the group consisting of alpha, beta, gamma, and deltatocopherols in its natural or synthetic (dl) forms; alpha, beta, gamma,and delta tocotrienols in its natural or synthetic (dl) forms, dl-alphatocopheryl derivatives, including dl-alpha tocopheryl esters,dl-alpha-tocopheryl acetate or succinate and d-alpha-tocopheryl acetateor dl-alpha tocopheryl phosphates; wherein said vitamin C is in the formselected from one or more of the group consisting of ascorbic acid,asorbates, calcium ascorbate, sodium ascorbate, dehydroascorbic acid andsalts, ascorbyl palmitate, ascorbyl phosphates and salts, ascorbylsulfates and salts, acylated ascorbic acid derivatives,6-bromo-6-deoxy-L-ascorbic acid, and ascorbate salts; wherein said ironis in the form selected from one or more of the group consisting ofelemental iron, in the form of a salt, chelated form, non-chelated form,chelated to an amino acid, carbonyl iron, ferrous gluconate, ferrousfumarate, polysaccharide iron complex, elemental polysaccharide iron,polysaccharide iron, ferrous (II)-bis-glycinate chelate, ferrous aspartoglycinate, ferrous bisglycinate, ferrous bisglycinate hydrochloride,ferrous bisglycinate, elemental ferrous bisglycinate, ferrous sulfate,ferronyl (micronized), iron protein succinylate, carbonyl iron, Sumalateiron, Heme iron complex, as Ferrochel amino acid chelate, Heme ironpolypeptide as Proferrin-bovine source, as heme iron polypeptide (bovinesource) as sodium iron EDTA (Ferrazone), ferric ammonium citrate,elemental iron, and ferric pyrophosphate; wherein said zinc is in theform selected from one or more of the group consisting of elementalzinc, in the form of a salt, in a chelated form, in a non-chelated form,zinc acetate, zinc gluconate, zinc picolinate, zinc sulfate and zincoxide; wherein said copper is in the form selected from one or more ofthe group consisting of elemental copper, in the form of a salt, in achelated form, in a non-chelated form, cupric oxide, copper sulfate,copper gluconate, copper citrate, cupric acetate, and alkaline coppercarbonate; wherein said magnesium is in the form selected from one ormore of the group consisting of elemental magnesium, in the form of asalt, in a chelated form, in a non-chelated form, magnesium acetate,magnesium carbonate, magnesium gluconate, magnesium chloride, magnesiumcitrate, magnesium silicate, magnesium stearate, magnesium sulfate,magnesium oxide, and magnesium chelated to an amino acid; wherein saidomega 3 fatty acids is in the form selected from one or more of thegroup consisting docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA)and α-linolenic acid (ALA); and wherein said iodine is in the formselected from one or more of the group consisting of iodide, elementaliodine, iodized salt, Lugol's iodine, sodium iodide, potassium iodide,potassium iodate, nascent iodine, and Nano-Colloidal Detoxified Iodine.10. The method of claim 1, wherein said vitamin D is in the form ofvitamin D3 and is present in an amount of about 1000 I.U. or 25 μg. 11.The method of claim 1, wherein said iodine is present in an amount ofabout 150 μg.
 12. The method of claim 1, wherein said vitamin B1 ispresent in an amount of about 1.6 mg.
 13. The method of claim 1, whereinsaid vitamin B6 is present in an amount of about 2.5 mg.
 14. The methodof claim 1, wherein said vitamin B12 is present in an amount of about 12μg.
 15. The method of claim 1, wherein said vitamin B2 is present in anamount of about 1.8 mg.
 16. The method of claim 1, wherein said vitaminB9 is present in an amount of about 1.0 mg.
 17. The method of claim 1,wherein said vitamin E is present in an amount of about 20 I.U.
 18. Themethod of claim 1, wherein said vitamin A is in the form of betacarotene and is present in an amount of about 1100 I.U. or about 660 μg.19. The method of claim 1, wherein said vitamin C is present in anamount of about 30 mg.
 20. The pharmaceutical composition of claim 1,wherein said vitamin B3 is in the form of nicotinamide and is present inan amount of about 15 mg.
 21. The method of claim 1, wherein said ironis present in an amount of about 29 mg.
 22. The method of claim 1,wherein said zinc is present in an amount of about 25 mg.
 23. The methodof claim 1, wherein said copper is present in an amount of about 2.0 mg.24. The method of claim 1, wherein said magnesium is present in anamount of about 20 mg.
 25. The method of claim 1, wherein said omega 3fatty acids comprises DHA and is present in an amount of about 200 mg.26. The method of claim 1, wherein said omega-3 fatty acids comprisesDHA, and wherein the source of DHA is algae oil.
 27. The method of claim26, wherein the source of the algae oil is microalgae Crypthecodiniumcohnii.
 28. The method of claim 1, wherein said pharmaceuticallyacceptable carriers include one or more selected from the groupconsisting of gelatin, sorbitol, glycerin, soybean oil, beeswax,dicalcium phosphate, lecithin oil, vegetable oil, and colorants.
 29. Themethod of claim 1, wherein said composition does not contain fish oils.30. The method of claim 1, wherein said vitamin B12 is present in anamount of about 6 μg to about 18 μg.
 31. The method of claim 1, whereinsaid vitamin C is present in an amount of about 15 mg to about 45 mg.32. The method of claim 1, wherein said iron is present in an amount ofabout 14.5 mg to about 43.5 mg.